title: Designing amino acid residues with single-conformations.
abstract: Drug design can benefit from the use of non-coded amino acids, such as alpha-amino isobutyric acids (Aib) or sarcosine (N-methyl-glycine). Non-coded amino acids can confer resistance to enzymatic degradation and increase the conformational stability of the peptides. We have simulated the conformational effects of combining N-methylation, bulky groups on the Calpha atom and/or thioamides using the class II CFF91 force field and our thioamide force field parameters. Although single amino acid substitutions (e.g. Aib) can restrict the available conformations, they do not necessarily lead to unique conformers, however, we predict that some of the amino acids described in this report will fold to a single phi, psi conformation (e.g. N-methylated and thioamide penicillamine). Several other amino acid/thiopeptide combinations were designed, which are predicted to prefer only two conformations. Novel amino acids of this type should prove useful for designing peptides with defined conformations.
authors.affiliation: Ludwig Institute for Cancer Research and Cooperative Research Centre for Cellular and Growth Factors, Melbourne, Victoria 3050, Australia.
authors.forename: Tran T
authors.initials: TT
authors.lastname: Tran
authors.forename: Herbert
authors.initials: H
authors.lastname: Treutlein
authors.forename: Antony W
authors.initials: AW
authors.lastname: Burgess
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D004151:Dipeptides / Q000737:chemistry*; D015195:Drug Design; D008745:Methylation; D008956:Models, Chemical; D011487:Protein Conformation; D012521:Sarcosine / Q000737:chemistry; D013854:Thioamides / Q000737:chemistry
chemical_list: D000596:Amino Acids; D000621:Aminoisobutyric Acids; D004151:Dipeptides; D013854:Thioamides; C100049:2-aminoisobutyric acid; D002244:Carbon; D012521:Sarcosine