DOI: 10.5281/zenodo.15094801
title: AANCHOR library: Amino Acid N/C-termini Hybrids Optimized for Receptors

description: G protein-coupled receptors (GPCRs) constitute a large family of pharmacological targets, with numerous therapeutics approved for clinical use. Within this family, peptide receptors are integral to the regulation of a wide array of physiological processes. To facilitate the design of small molecule ligands targeting peptide GPCRs, we have developed a comprehensive library of 4.7 billion compounds. The AANCHOR (Amino Acid N/C-termini Hybrids Optimized for Receptors) library consists of 20 proteinogenic amino acids along with their corresponding carboxamide and N-formylated derivatives that are linked through amidation at their respective C- and N-termini with commercially available building blocks. Further details regarding the datasets and the methodology can be found in our publication:

“PAPER TITLE” (DOI: xxxxx).

We encourage you to download and utilize these datasets in your research projects focused on identifying ligands of peptide-binding targets. We kindly request that you cite our publication and datasets in any work that incorporates them. Thank you for your interest in the AANCHOR library!

USAGE:

File structure:

Each tar.bz2 compressed file contains all terminal derivatives of the amino acid specified in the file name. Upon decompression, two subdirectories can be found: chemspace/ and real/, which denote the source of the coupling reagent. Within each vendor subdirectory, SMILES files are available. The naming convention of the SMILES files reflects the amino acid, the type of reactant, and the heavy atom count of the products contained within the file (e.g., Phe-NH2_monoester_28HA.smi indicates the products resulting from the amidation of phenylalanine amide with an ester, yielding molecules with a heavy atom count of 28). Each SMILES file comprises two columns: the SMILES string of the product and the identifier of the reactant utilized in its synthesis.

Product synthesis:

Upon selection of the desired amino acid derivatives, the corresponding amino acid building block (listed in the file amino_acid_BBs.smi together with their respective CAS identifiers) and the reactant should be purchased. Briefly, the amines will react with carboxylates or acyl halides specified in the SMILES files. The products can then be obtained via amide coupling, which may be performed through in-house synthesis. Briefly, a mixture of the reactant, protected amino acid, a base (e.g. triethylamine), and a suitable coupling reagent (e.g. TBTU) are mixed. Following the completion of the reaction, the protecting group of the amino acid can be removed. For a detailed example of leucine derivatization, please refer to our publication in the Supplementary Methods: Chemistry.
description: It is important to note that utilizing the monoester category may result in certain artifacts. For instance, a reactant specified in the file that could facilitate the synthesis of a desired amino acid derivative may be a relatively large molecule on the alcohol side. However, only the acyl group (e.g., propionate) is relevant to the reaction. Therefore, it is advisable to consider employing a simpler alternative reactant to optimize resource utilization.