title: Molecular modeling in the design of peptidomimetics and peptide surrogates.
abstract: The most important natural sources of new leads are plant extracts, bacterial broths, animal venoms and peptides isolated from living organisms. However, only the three first have been used extensively in the development of new therapeutic agents. This is probably due to the low pharmacological profile exhibited by peptides, that requires a lengthy transformation to make them suitable as new leads. In contrast, bioactive compounds isolated from the other sources are regularly closer to be used as lead compounds. Nevertheless, the sources for compounds of this category are nowadays scarce. In contrast, there are new bioactive peptides discovered quite often and reported as ligands for different receptors. Under these circumstances peptides appear as an attractive source of prospective new leads. In order to reduce the time involved in the design of a potential lead from a peptide, molecular modeling tools have been developed in the last few years. The purpose of the present work is to review the different techniques available and to report various successful examples of design of new peptidomimetics published in the literature.
authors.affiliation: Dept. d'Enginyeria Química, Technical University of Catalonia, ETS d'Enginyeria Industrial de Barcelona, Av. Diagonal, 647; 08028 Barcelona, Spain. Juan.jesus.perez@upc.es
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Perez
authors.forename: Francesc
authors.initials: F
authors.lastname: Corcho
authors.forename: Oriol
authors.initials: O
authors.lastname: Llorens
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D015195:Drug Design; D051231:Farnesyltranstransferase; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors
chemical_list: D017320:HIV Protease Inhibitors; D010455:Peptides; D000804:Angiotensin II; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D013917:Thrombin