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A Lasso‐Inspired Bicyclic Peptide: Synthesis, Structure and Properties
Author(s) -
MartinGómez Helena,
Albericio Fernando,
TullaPuche Judit
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201803899
Subject(s) - bicyclic molecule , peptide , chemistry , covalent bond , cyclic peptide , combinatorial chemistry , stereochemistry , biochemistry , organic chemistry
The chemical synthesis of a bicycle inspired by the natural lasso peptide sungsanpin using a combination of solid‐phase and in‐solution chemistries is described. The bicyclic‐derived topoisomer was designed by introducing a covalent linkage between the ring and the loop, which allowed the tying of these two parts of the peptide, rendering the bicyclic structure. Several structural techniques, such as MS fragmentation, ion‐mobility and NMR spectroscopic analysis were used to characterize the bicycle. Ion‐mobility spectroscopy studies revealed that it showed lasso‐like behavior. Its 3D structure was predicted on the basis of the NMR restraints. In addition, the high proteolytic and thermal stability of the bicycle potentially make it a suitable scaffold for epitope grafting.