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Integrating the intrinsic conformational preferences of noncoded alpha-amino acids modified at the peptide bond into the noncoded amino acids database

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Recently, we reported a database (NCAD, Non-Coded Amino acids Database; http://recerca.upc.edu/imem/index.htm) that was built to compile information about the intrinsic conformational preferences of non-proteinogenic residues determined by quantum mechanical calculations, as well as bibliographic information about their synthesis, physical and spectroscopic characterization, the experimentally-established conformational propensities, and applications (J. Phys. Chem. B 2010, 114, 7413). The database initially contained the information available for α-tetrasubstituted α-amino acids. In this work, we extend NCAD to three families of compounds,which can be used to engineer peptides and proteins incorporating modifications at the -NHCO-peptide bond. Such families are: N-substituted α-amino acids, thio-α-amino acids, and diamines and diacids used to build retropeptides. The conformational preferences of these compounds have been analyzed and described based on the information captured in the database. In addition, we provide an example of the utility of the database and of the compounds it compiles in protein and peptide engineering. Specifically, the symmetry of a sequence engineered to stabilize the 310-helix with respect to the α-helix has been broken without perturbing significantly the secondary structure through targeted replacements using the information contained in the database.

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REVILLA-LOPEZ, Guillem, RODRIGUEZ-ROPERO, Francisco, CURCÓ CANTARELL, David, TORRAS, Juan, CALAZA, M. isabel, ZANUY GOMARA, David, JIMENEZ, Ana i., CATIVIELA, Carlos, NUSSINOV, Ruth, ALEMÁN, Carlos. Integrating the intrinsic conformational preferences of noncoded alpha-amino acids modified at the peptide bond into the noncoded amino acids database. _Proteins: Structure_. Function. Vol.  and Bioinformatics, núm. 2011, pàgs. 79. [consulta: 26 de febrer de 2026]. ISSN: 0887-3585. [Disponible a: https://hdl.handle.net/2445/127754]

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