A Computational Study of the Mechanism of Succinimide Formation in the Asn–His Sequence: Intramolecular Catalysis by the His Side Chain
Department of Natural Products, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
In the course of our ongoing efforts to identify marine-derived bioactive compounds, the marine cyanobacterium Moorea producens was investigated. The organic extract of the Red Sea cyanobacterium afforded one new cerebroside, mooreaside A (1), two new nucleoside derivatives, 3-acetyl-2′-deoxyuridine (2) and 3-phenylethyl-2′-deoxyuridine (3), along with the previously reported compounds thymidine (4) and 2,3-dihydroxypropyl heptacosanoate (5). The structures of the compounds were determined by different spectroscopic studies (UV, IR, 1D, 2D NMR, and HRESIMS), as well as comparison with the literature data. Compounds 1–5 showed variable cytotoxic activity against three cancer cell lines.
Nucleosides and cerebrosides are found in both terrestrial and marine organisms. Cerebrosides are composed of a hydrophobic part named ceramide, which is linked to one sugar moiety [1]. Cerebrosides play an important role in major cellular processes including growth, morphogenesis and cell differentiation. They also affect cell signaling by controlling the assembly and specific activities of plasma membrane proteins [2,3]. Nucleosides are derivatives of glycosylamines, which are central metabolites in all life forms [4]. Nucleotides, the building block of DNA and RNA are composed mainly of nucleosides with at least one phosphate group. Nucleoside-derived compounds are used effectively in treatment of tumors, viral infections and malignant neoplasms [5,6].
Marine cyanobacteria are vital producers of diverse chemical entities with significant bioactivities [7,8,9,10]. The genus Moorea (formerly Lygnbya) [11] has been proven to be a rich source for novel bioactive compounds of different classes [11,12]. Cyanobacteria derived compounds display a wide range of biological activities including those that are antimicrobial, antiproliferative, anticancer, antifeedant, antifungal, and anti-inflammatory [13,14,15,16,17]. Previous work on the Red Sea cyanobactrium Moorea producens revealed the presence of nitrogen-containing compounds, polyketides and peptides [16,17]. In continuation of our ongoing interest to allocate new bioactive compounds from Red Sea marine cyanobacteria [16,17,18,19], we here focus on the Red Sea strain of the cyanobacterium Moorea producens. In this paper, we reported the isolation and structure determination of a new cerebroside, mooreaside A (1), two new nucleoside derivatives, 3-acetyl-2′-deoxyuridine (2) and 3-phenylethyl-2′-deoxyuridine (3), along with the known compounds thymidine (4) and 2,3-dihydroxypropyl heptacosanoate (5) from the organic extract of the marine cyanobacterium Moorea producens. The structures of the compounds were determined using different spectroscopic techniques. The cytotoxic activity of the compounds against three cancer cell lines will be discussed.
Samples of M. producens were extracted with a mixture of MeOH/CH2Cl2 (2:1). The organic extract was subjected to chromatographic separation on normal SiO2, Sephadex LH-20, and RP-18 columns to provide three new compounds 1–3 and two known compounds 4 and 5 (Figure 1). The isolated compounds were evaluated for their cytotoxic activity.
Compound 1 (Figure 1) was obtained as a colorless amorphous powder. Its molecular formula was suggested as C48H93NO8 on the basis of the HRESIMS quasi-molecular ion peak at m/z 812.6982 [M + H]+ and 1H- (Figures S1–S3) and 13C-NMR (Figures S4 and S5) spectral analyses, requiring three degrees of unsaturation. Its IR spectrum showed characteristic absorption bands at 3435 (hydroxyl), 3320 and 1635 (amide), 3005 and 960 (olefinic), and 1150 (C–O) cm−1, suggesting the cerebroside nature of 1 [20,21,22,23]. The 1H-NMR spectrum of 1 showed two signals at δH 5.35 (dt, J = 15.3, 7.6 Hz, H-5) and 5.37 (dt, J = 15.3, 7.1 Hz, H-6) in 1H-NMR spectrum characteristic for the presence of a di-substituted olefinic moiety (Table 1) which was supported y COSY correlation (Figure S6). These protons correlated to the carbon signals at δC 129.9 and 128.8, respectively, in the HSQC spectrum (Figure S7). The trans (E) configuration of the double bond was proven by the large vicinal coupling constant value (J5,6 = 15.3 Hz) and the chemical shifts of the carbons next to the double bond at δH 32.2 (C-4) and 32.0 (C-7) [24,25,26]. The location of the olefinic moiety at C-6/C-7 was established based on the HMBC cross peaks from H-5 to C-3, C-4, and C-7 and from H-6 to C-4, C-5, and C-7 (Figure S8). In the 1H, 13C, and multiplicity-edited HSQC spectra, the signals at δH 4.28 (d, J = 7.7 Hz, H-1′′)/δC 104.0 (C-1′′) revealed the presence of a β-glucopyranoside moiety. This was also confirmed by the ESIMS fragment ion peak at m/z 633 [MH − Glc]+. The attachment of the glucose moiety at C-1 was established by the downfield shift of C-1 (δC 68.5) and HMBC correlation of H-1′′ (δH 4.28) with C-1. Moreover, the 1H-NMR spectrum of 1 showed signals at δH 3.61 (m, H-3), 3.97 (m, H-2), 3.91 and 3.74 (each m, H-1) attributable to oxymethine, NH-bonded methine, and oxymethylene groups, respectively. They correlated with the carbon signals at 73.4 (C-3), 59.3 (C-2), and 68.5 (C-1) in the HSQC spectrum. 1H-1H COSY cross peaks were observed between the NH proton (δH 7.51) and H-2, which coupled to H-1 and H-3, suggesting the presence of hydroxyl group in the long chain base. This was further confirmed by the HMBC correlations of H-1 to C-2 and C-3, H-2 to C-1, C-3, and C-4, H-3 to C-1 and C-2, and 2-NH to C-2 and C-3 (Figure 2). Comparing 13C-NMR spectrum of 1 with those of glucosyl-erythro-ceramide and glucosyl-threo-ceramide, proved the erythro configuration at C-2 and C-3 in the sphingosine part of 1 [27,28,29,30,31,32]. The length of the fatty acid chain (C-1′→C-25′) and base chain (C-1→C-17) was determined by the ESIMS. The EIMS spectrum of 1 showed characteristic fragment ion peaks at m/z 380 [CH3(CH2)23CONH]+, 365 [CH3(CH2)23CO]+, 337 [CH3(CH2)23]+, 225 [CH3(CH2)10-CH=CH-CH2(CHOH)]+, 181 [CH3(CH2)10-CH=CH]+, and 155 [CH3(CH2)10]+ (Figure 3), supporting the chain lengths of 1. Methanolysis of 1 gave long chain base (LCB) and fatty methyl ester (FAME). The FAME in the n-hexane layer was identified as pentacosanoic acid methyl ester based on the GCMS molecular ion peak at m/z 396 [M]+. The LCB showed an EIMS molecular ion peak at m/z 285 [M]+, corresponding to (2S,3R,E)-2-aminoheptadec-5-ene-1,3-diol. Based on the above evidence and discussion, compound 1 was assigned as N-((2S,3R,5E)-3-hydroxy-1-O-((β-d-glucopyranosyl)heptadec-5-en-2-yl)pentacosanamide. Compound 1 was generically named mooreaside A.
Compound 2 (Figure 1) was obtained as a white powder. Its HRESIMS gave a quasi-molecular ion peak at m/z 271.0927 [M + H]+, consistent with a molecular formula C11H14N2O6, requiring six degrees of unsaturation. The IR spectrum of 2 showed absorption bands at 3394 (hydroxyl) and 1693 (amide carbonyl) cm−1. These data in conjunction with characteristic UV absorption bands at λmax 253 and 268 nm along with 1H NMR spectrum (Figures S9–S11) suggested the presence of uracil moiety in 2. The 13C (Figure S12) and multiplicity-edited HSQC (Figure S13) spectra of 2 showed signals for 11 carbons including one methyls, two methylenes, five methines, and three quaternary carbonyls at δC 151.7 (C-2), 162.8 (C-4), and 183.4 (C-8). The 1H-1H COSY spectrum (Table 2) showed two ortho-coupled protons at δH 5.69 (d, J = 8.5 Hz, H-5) and 7.98 (d, J = 8.5 Hz, H-6). These protons correlated to the carbon signals at δC 102.6 and 142.5, respectively in the HSQC, indicating the presence of uracil moiety in 2. This was confirmed by the HMBC (Figure S14) cross peaks from H-5 to C-4 and C-6 and from H-6 to C-2 and C-4. Moreover, the 1H- and 13C-NMR signals at δH 6.27 (t, J = 6.8 Hz, H-1′)/δC 86.6 (C-1′), 2.28 (m, H2-2′)/41.4 (C-1′), 4.38 (m, H-3′)/72.2 (C-3′), 3.89 (m, H-4′)/89.0 (C-4′), and 3.75 (m, H-5′a) and 3.71 (m, H-5′b)/62.8 (C-5′) supported the presence of 2′-deoxyribose moiety [33] in 2. The connectivity of this moiety at N-1 of the uracil moiety was established by the HMBC cross peaks from H-6 to C-1′ and from H-1′ to C-2 and C-6. Furthermore, signals for an acetyl group at δH 1.95 (3H, s, H-2′′)/δC 23.5 (C-2′′) and 183.4 (qC, C-1′′) were observed [34]. This was confirmed by the ESIMS fragment ion peak at m/z 228 [MH – COCH3]+. Based on the 13C chemical shifts, the acetyl group was assigned at N-3 of the uracil moiety, completing the molecular formula of 2 and the degrees of unsaturation. Consequently, 2 was assigned as 3-acetyl-2′-deoxyuridine and is reported here as a new natural product.
Compound 3 (Figure 1) was obtained as white amorphous powder with a molecular formula C17H20N2O5 as determined from its HRESIMS quasi-molecular ion peak at m/z 333.1446 [M + H]+, requiring nine degrees of unsaturation. The 1D and 2D-NMR (Figures S15–S20) spectral data (Table 2) of 3 were quite similar to those of 2 except the absence of the signals associated with acetyl group at N-3. Instead, new signals at δH/δC 7.35 (2H, d, J = 8.5 Hz, H-5′′,7′′)/130.0 (C-5′′,7′′), 7.27 (2H, brd, J = 8.5 Hz, H-4′′,8′′)/129.8 (C-4′′,8′′), 7.25 (1H, t, J = 8.5 Hz, H-6′′)/128.3 (C-6′′), 2.95 (2H, t, J = 7.6 Hz, H-2′′)/34.7 (C-2′′), and 3.16 (2H, t, J = 7.6 Hz, H-1′′)/34.7 (C-1′′) were observed. The signals suggested the presence of a N-bonded phenylethyl moiety. This was established by 1H-1H COSY cross peaks, and further confirmed by HMBC correlations (Figure 2) from H-2′′ to C-4′′/C-8′′ and C-1′′, and from H-1′′ to C-2′′ and C-3′′. The HMBC cross peaks of H-1′′/C-2 and H-1′′/C-4 supported the placement of phenylethyl moiety at N-3. Moreover, the ESIMS of 2 gave a characteristic fragment ion peak at m/z 228 [MH − CH2CH2C6H5]+, indicating the loss of a phenylethyl moiety [35]. Thus, compound 3 was assigned as 3-phenylethyl-2′-deoxyuridine and is considered a new natural product.
The known compounds were identified as thymidine (4) [36] and 2,3-dihydroxypropyl heptacosanoate (5) [37,38] by analysis of their spectroscopic data and comparison with those in the literature.
The compounds were evaluated for their cytotoxic activities against three cancer cell lines, including colorectal carcinoma (HCT-116, ATCC CCL-247), hepatocellular carcinoma (HepG2, ATCC HB-8065), and breast cancer (MCF-7, ATCC HTB-22). Compounds 1–3 showed moderate activity towards MCF-7 cancer cell line. Meanwhile, they were inactive towards HCT-116 and HepG2 cancer cell lines (Table 3).
Optical rotations were measured on a JASCO DIP-370 digital polarimeter (Jasco Co., Tokyo, Japan) at 25 °C at the sodium D line (589 nm). UV spectra were recorded on a Hitachi 300 spectrometer (Hitachi High-Technologies Corporation, Kyoto, Japan). The IR spectra were acquired with a Shimadzu Infrared-400 spectrophotometer (Shimadzu, Kyoto, Japan). EIMS was recorded on a JEOL the mass route JMS.600H mass spectrometer (JEOL USA, Inc., Peabody, MA, USA). HRESIMS spectra were performed on a Micromass Qtof 2 mass spectrometer (Bruker, Rheinstetten, Germany). GCMS analysis was performed on GCMS Hewlett-Packard 5890 GC (Hewlett-Packard, Wilmington, DE, USA) equipped with a mass-selective detector MSD 5970 MS, a split injector and a fused-silica HP-5 column (25 m × 0.2 mm; i.d. 0.33 mm film); column temp. 230 °C, carrier N2, flow rate 30 mL/min. NMR spectra were determined on Bruker Ascend™ 850 (850 MHz) (Bruker BioSpin, Billerica, MA, USA) using CD3OD and CDCl3 as solvent. The HPLC separation was performed on a RP-18, 250 × 10 mm, 5 μm Phenomenex Luna column using H2O/ACN as mobile phase, detected at 220 nm with a flow rate of 2.0 mL/min. Column chromatographic separations were performed on SiO2 60 (0.04–0.063 mm, Merck, Darmstadt, Germany), Sephadex LH-20 (0.25–0.1 mm, Merck), and RP-18 (0.04–0.063 mm, Merck). Pre-coated SiO2 60 F254 plates (Merck) were used for TLC. Compounds were detected by UV absorption at λmax 255 and 366 nm followed by spraying with p-anisaldehyde/H2SO4 reagent and heating at 110 °C for 1–2 min.
The marine cyanobacterium Moorea producens was collected from the Red Sea by hand at 1 m depth near Jeddah, Saudi Arabia. The cyanobacterium was identified by Dr. Ali Gab-Alla, Faculty of Science of Suez Canal University. A voucher sample was kept at Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University under the registration code No. 2013-LM5.
The freeze-dried cyanobacterium M. producens (35 g) was extracted at room temperature with a mixture of MeOH/CH2Cl2 (2:1, 1 L × 4). The combined extracts were evaporated under reduced pressure to give a greenish organic extract. The extract (980 mg) was subjected to flash SiO2 column using n-hexane/EtOAc/MeOH gradients to give 7 fractions (F1–F7). Fraction F2 (n-hexane/EtOAc 8:2, 65 mg) was chromatographed over SiO2 column (35 g × 50 cm × 2 cm) using n-hexane/EtOAc (97:3 to 90:10) to give impure 5, which was purified by C18 semi-preparative HPLC column using 30% ACN to give 5 (5.3 mg). Fraction F4 (55 mg, EtOAc) was chromatographed over SiO2 column (30 g × 50 cm × 2 cm) using CHCl3/MeOH (95:5 to 85:15) elution afforded impure 1, which further purified on C18 HPLC semi-preparative column using 55% ACN to give pure 1 (9.6 mg). Sephadex LH-20 column chromatography (50 g × 50 cm × 3 cm) of fraction F6 (68 mg) using MeOH as solvent system gave impure 2 and 3. Final purification of the two compounds was achieved on RP-18 column (60 g × 50 cm × 3 cm) using MeOH/H2O (50:50 to 90:10) elution to give 2 (4.3 mg) and 3 (3.2 mg). HPLC purification of F7 (35 mg) on C18 HPLC semi-preparative column using 60% ACN gave 4 (3.5 mg).
The isolated compounds (1–5) were evaluated for their cytotoxic activity against colorectal carcinoma (HCT-116), hepatocellular carcinoma (HepG2), and breast cancer (MCF-7). The cells were obtained commercially from ATCC. The cytotoxicity was evaluated by the sulforhodamine B (SRB) assay, as described previously [39]. Doxorubicin was used as positive control drug (Table 3).
Compound 1 (4.5 mg) was treated with 6 mL of 1N HCl in MeOH at 90 °C for 15 h in a sealed ampoule. The reaction mixture was diluted by adding 20 mL of distilled water, then extracted with n-hexane (3 × 15 mL) to give a corresponding FAME, which was identified by GCMS. The aqueous layer was evaporated to dryness and subjected to Sephadex LH-20 using CHCl3:MeOH (10:90) to give LCB and sugar. The base was analyzed by EIMS [22].
In conclusion, the investigation of the Red Sea strain of the marine cyanobacterium Moorea producens led to the isolation of a new cerebroside (1) and two new nucleoside derivatives (2 and 3), along with two known compounds (4 and 5). Their structures were determined using extensive spectroscopic studies. Compounds 1–3 showed moderate cytotoxic activity against breast cancer cell lines.
The following are available online at https://www.mdpi.com/1420-3049/21/3/324/s1, Figure S1: 1D and 2D NMR spectra of compounds 1–3.
This project was funded by the National Plan for Science, Technology and Innovation (MAARIFAH)—King Abdulaziz City for Science and Technology—the Kingdom of Saudi Arabia–award number (11-BIO1555-03). The authors also, acknowledge with thanks Science and Technology Unit, King Abdulaziz University for technical support.
© 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).
Epigenetics of Neurodevelopmental Disorders Comes of Age with Roles in Clinical and Educational Applications
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, Queensland 4102, Australia
Received: 2 August 2018 / Revised: 29 August 2018 / Accepted: 6 September 2018 / Published: 12 September 2018
The insulin like growth factor 1 (IGF-1) and its receptor (IGF-1R) facilitate tumor proliferation and progression. Tanshinone IIA (TSN) is an active diterpene quinone isolated from the roots of the herbal plant Salvia miltiorrhiza. TSN inhibits the proliferation of various types of cancer cells but its role in the IGF-1R-induced proliferation of pheochromocytoma (PC12) cells and the potential mechanisms are largely unknown. This study aims to investigate the anti-proliferative effect of TSN in PC12 cells and its role on IGF-1R signaling transduction. PC12 cells were treated with IGF-1 with or without TSN, methyl thiazolytetrazolium (MTT) assay, and cell counting kit-8 and flow cytometry were used to evaluate the proliferation of PC12 cells. The role of TSN on the apoptosis of PC12 cells were detected by flow cytometry as well. The effects of TSN and IGF-1 on the phosphorylation of IGF-1R, protein kinase B (Akt), extracellular-signal related kinase 1/2 (ERK1/2) and other downstream targets were analyzed by Western blotting analysis. Our results showed that IGF-1 promoted the growth of PC12 cells in a dose-dependent manner and increased the phosphorylation of IGF-1R, whereas TSN attenuated the effect of IGF-1. Interestingly, TSN did not induce cell apoptosis in PC12 cells. Moreover, TSN attenuated the phosphorylation of Akt and ERK1/2 induced by IGF-1, and the phosphorylation of glycogen synthase kinase-3β, forkhead box O3a (FOXO3a) and c-Raf were also inhibited by TSN. Furthermore, TSN inhibited cell growth induced by IGF-1 and blocked the activation of IGF-1R in SH-SY5Y cells. Taken together, TSN has an inhibitory effect on the proliferation of PC12 cells via down-regulation of the phosphorylated IGF-1R and its downstream signaling. View Full-Text
Factors Affecting the Effectiveness of Inorganic Silicate Sealer Material through Multi-Quality Characteristics
Department of Harbor and River Engineering, National Taiwan Ocean University, 2 Pei-Ning Road, Keelung, 20224, Taiwan
This study investigates the effectiveness of concrete protection with two inorganic silicate sealer materials (ISSMs). The Taguchi method and grey relational analysis (GRA) have been used to identify the key factors influencing concrete protection provided by the surface treatment. Seven control factors with two levels were selected. By using the orthogonal array L12 (27), 12 experiments are chosen and four tests—the compressive strength test, resistivity test, absorption test and permeability test—were performed. Results have shown that the major factors affecting the protection effectiveness of ISSM are the water-binder ratio of mortar substrate, age of substrate for sealer application, addition of pozzolanic material and sealer type. View Full-Text
The forces of corporatism won another battle last week as the Montgomery County Council rejected a proposal to block the county from giving $4 million to a developer that is building a Costco in Wheaton. Deals like this are problematic for many so many reasons that I can’t sum them up in one blog, so today I’m going to focus on the idea that they are needed to create jobs. On Wednesday I’ll talk about their effect on political corruption.
Politicians in both parties love “economic development” deals. It gives politicians the appearance of doing something to create jobs, even though government-directed economic growth schemes have a long history of failure. The appearance, not the reality, is what’s important in politics. It’s much better for politicians to allocate money to a business, get their picture in the paper for a ribbon cutting, than to pursue true pro-growth policies.
One state that has been in the forefront of government-sponsored “economic development” is Michigan. As Michael Lafaive, who works for the Mackinac Center in that state, points out, a study done by the Citizens Research Council (CRC) on tax abatements indicates there are few benefits (the logic applies to other subsidies, too):
…CRC noted in a different report that the tax abatement is used most by local governments with the highest taxes. In other words, tax abatements may be necessary to avoid losing businesses to low-tax areas. Of course, other factors may play a role in business development, too. Low-tax areas may also have great schools and low crime rates, which no doubt play an important role in business and location decisions.
Does the tax abatement method meet with success? Not as much as if local officials simply would keep taxes low in the first place. CRC found that greater economic growth takes place in jurisdictions where taxes are low and which consequently grant fewer abatements. CRC found that "50% of high tax jurisdictions experienced low growth, whereas only 18% of the low tax jurisdictions and 19% of the medium jurisdictions experienced low growth." This suggests that keeping the economic playing field level and offering no special favors yields better results than government picking winners and losers through the use of tax abatements.
In a previous story on the Costco deal, Council member George Leventhal said that “the public needs to understand it’s what’s necessary to attract jobs and investment to the county.” If that’s true, then it’s a pretty damning indictment of the business climate in Montgomery County. If the only way you can get job creation is to have the government hand out subsidies, then your county is in real trouble.
In fact, these incentives are another symptom of the problems caused by the government for those looking to start or expand businesses in Montgomery County. The government officials want to micromanage the decisions of business owners and consumers, so they enact a variety of laws and regulations to restrict the choices of business owners and consumers. Then they turn around and give subsidies to favored businesses.
As Lafaive notes, these types of incentives distort the economy: “public-sector intervention simply displaces private-sector initiative. It sends private businesses scrambling for the biggest tax abatement they can get, instead of looking for ways to satisfy the desires of their communities and make more consumer-friendly products.”
Moving towards a system of less intrusive regulations and a low, flat tax rate would do much more to create jobs in Montgomery County than its policy of handing out cash to a few politically-favored businesses. But this would mean that politicians would have to give up a lot of their power to tell others how to run their lives. I don’t know how realistic that is for a jurisdiction like Montgomery County.
The nation’s first public, urban, college-prep boarding school emphasizes academic excellence and personal development. A six-year evaluation using SEED’s admission lotteries found that SEED DC raised lottery winners’ test scores but did not increase the on-time graduation rate or reduce teen pregnancy or involvement in the criminal justice system.
MDRC President Gordon Berlin draws lessons from MDRC’s implementation of the first social impact bond (SIB) project in the United States, providing valuable insights into the inner workings of SIB deals and explaining the challenges and the potential of this impact investing model.
The Workforce Innovation and Opportunity Act (WIOA) emphasizes targeting out-of-school youth with training and services that are employer driven and linked to labor market demand. Drawing upon available research and on-the-ground experience, this paper summarizes existing knowledge that can guide implementation of key WIOA provisions for serving out-of-school youth.
Improving the employment outlook of disadvantaged young people on a large scale will require a stronger focus on engaging private employers on potential solutions. On June 4, 2014, MDRC and The Rockefeller Foundation convened a group of experts to discuss such demand-driven approaches.
The Great Recession took a toll on the already dim economic prospects of low-income 16- to 24-year-olds who face structural barriers to employment. Evidence indicates that involvement of employers in devising education, training, and work experiences that meet labor market demands should be a key component of any policy response.
In this essay, adapted from remarks made to the Growth Philanthropy Network/Social Impact Exchange 2014 Conference on Scaling Impact, MDRC President Gordon Berlin explains why developing reliable evidence of effectiveness is critical when expanding programs to a large scale.
A review of high-quality studies, this paper highlights interventions — in education, employment and training, and second-chance programs — that have demonstrated positive results for young men of color. It comes as policymakers and philanthropies focus new attention on investing more to build opportunities for these young men.
MDRC hosted a recent colloquium to celebrate our 40th anniversary and the contributions of former Board Chair Robert Solow. This issue focus summarizes a panel presentation, featuring Frank Levy, Richard J. Murnane, Cecilia E. Rouse, and Ronald F. Ferguson, about current challenges in education and how MDRC’s research can help address them.
This brief essay by Gordon Berlin, first published by the Nonprofit Finance Fund, builds on MDRC’s experience as the intermediary in the nation’s first operational Social Impact Bond to describe three broad challenges facing the Pay for Success movement as it moves from promising concept to on-the-ground implementation.