## 3 Results and Discussion
### Functionalization of the Hydrophobic Block: PLA-Gal  
Acid end-capped PLA of two different molecular weights (1-5 and 5-10 KDa) was functionalized by introducing an alkyne terminal group. The introduction of a triple bond gives access to a virtually infinite possible post-polymerization functionalization by the use of orthogonal click reactions such as Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition of alkynes and azides (CuAAC) [12], or thiol\(-\)yne addition [13]. Propargylamine was chosen as alkyne donor because of its reactivity but also because the formation of an amide linkage was preferred over the ester with propargyl alcohol which was found to be not sufficiently  
Figure 2: (**A**) \({}^{1}\)H NMR spectra of MeO-PEG\({}_{2000}\)-PBA in DMSO-\(d_{6}\) (400 MHz) and attribution of the signals to the structure. “\(t\)” signal has been attributed to free pinacol residue. (**B**) Comparison of the characteristic peaks in the \({}^{1}\)H NMR spectra of MeO-PEG\({}_{2000}\)-PBA, MeO-PEG\({}_{2000}\)-PBAPin and MeO-PEG\({}_{2000}\). Note the appearance of the peak at \(\sim\)4.1 ppm relative to the methylene of the esterified end of MeO-PEG\({}_{2000}\)-PBAPin, still found in the spectrum of the deprotected derivative MeO-PEG\({}_{2000}\)-PBA (panel in the middle), the methyl signal of the pinacol at 1.3 ppm in the spectrum of MeO-PEG\({}_{2000}\)-PBAPin (right panel), and the aromatic protons of PBA in both MeO-PEG\({}_{2000}\)-PBAPin and MeO-PEG\({}_{2000}\)-PBA spectra (left panel).  
stable in water (data not shown). A reasonable stability of derivatives is relevant to easily follow the condensation of the two blocks without the interference of the hydrolysis of the end-groups on them. Furthermore, the boiling point of propargylamine is 83 \({}^{\circ}\)C, and this allows us to \"strip\" it off by vacuum, avoiding additional workup procedures to remove potential unreacted traces, which benefits its cost-effectiveness. The reaction involved the use of EDC-HCl and NHS as coupling agents. Despite the use of two molar excess of the reagents compared to PLA, a complete alkynylation of the free acid ends of PLA chains was not achieved in both cases. The degree of functionalization (DD mol\(\%\)) was estimated by \({}^{1}\)H NMR by comparing the integral of the signal of the -C-H next to the terminal hydroxyl group of the PLA chain at 4.2 ppm, with the signal at 3.9 of the methylene protons of the propargylamine and resulted to be equal to 68.9 \(\pm\) 4.9\(\%\) and 67\(\%\) for PLA-Alk\({}_{1-5\text{kDa}}\) and PLA-Alk\({}_{5-10\text{kDa}}\), respectively.  
The two propargylated products were used as a substrate for the conjugation of an azide derivative of galactose. The presence of azide in position 6 of the modified sugar makes possible to use it in copper catalyzed [3 + 2] azide-alkyne cycloaddition (CuAAC), attributable to the group of \"click\" reactions. In our protocol, we used CuBr/ascorbic acid catalytic system in DMF. After overnight incubation at room temperature, a quantitative conversion of the starting alkynes into galactosylate moieties was obtained. This was true for both molecular weight ranges. The products, PLA-Gal\({}_{1-8\text{kDa}}\) and PLA-Gal\({}_{5-10\text{kDa}}\), were characterized by \({}^{1}\)H NMR. A representative spectrum with signal attribution is shown in Figure 3. The DD mol\(\%\) in Gal was around 30\(\%\) for both PLA-Gal\({}_{1-5\text{kDa}}\) and PLA-Gal\({}_{5-10\text{kDa}}\), respectively.  
Figure 3: (**A**) \({}^{1}\)H NMR spectrum of PLA-Gal in DMSO-\(d_{6}\) and signal attribution; (**B**) detail of PLA, PLA-Alk and PLA-Gal spectra in the alkyne proton region (2.15 ppm). Note the complete disappearance of the signal after the click reaction. Spectral signal and structural elements are correlated by lowercase letters.  
ATR FT-IR spectra of the products did not show significant differences compared with native PLA and are reported in Figures S3 and S4 in Supplementary Material.