MODELING CONSTRAINED CALCITONIN-GENE-RELATED PEPTIDE ANALOGS

Citation
Jml. Hakala et al., MODELING CONSTRAINED CALCITONIN-GENE-RELATED PEPTIDE ANALOGS, Protein engineering, 9(2), 1996, pp. 143-148
Citations number
18
Categorie Soggetti
Biology
Journal title
ISSN journal
02692139
Volume
9
Issue
2
Year of publication
1996
Pages
143 - 148
Database
ISI
SICI code
0269-2139(1996)9:2<143:MCCPA>2.0.ZU;2-I
Abstract
The calcitonin gene-related peptide (CGRP) is a 37-residue peptide wit h pronounced physiological activities, making it an interesting lead f or drug development, In our previous work, we designed constrained ana logues of the peptide. The biological activities of these proved that the disulfide bridges created favoured the active conformations of the peptide. Here we report the molecular modelling of the conformation o f domains involved in receptor activation. Our approach was to create sets of possible conformations for three differently constrained bioac tive regions by a random search of conformational space and molecular modelling. The conformations were compared, and those allowed for all derivatives were considered relevant for receptor activation. This app roach resulted in one favoured group of conformations characterized by an inverse gamma-turn followed by a gamma-turn, defining the conforma tion of the tripeptide region with a similar sequence in all active an alogues. The models may also be used for the design of peptide and non -peptide analogues of CGRP.