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Cover Picture: Reconstructing the Discontinuous and Conformational β1/β3‐Loop Binding Site on hFSH/hCG by Using Highly Constrained Multicyclic Peptides (ChemBioChem 1/2015)
Author(s) -
Smeenk Linde E. J.,
TimmersParohi Drohpatie,
Benschop Joris J.,
Puijk Wouter C.,
Hiemstra Henk,
van Maarseveen Jan H.,
Timmerman Peter
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201490067
Subject(s) - protein data bank (rcsb pdb) , chemistry , peptide , binding site , protein tertiary structure , epitope , disulfide bond , stereochemistry , protein structure , cyclic peptide , biology , biochemistry , antibody , immunology
The cover picture shows the X‐ray crystal structure of hCGβ (the “pregnancy hormone”, in blue) in complex with a monoclonal antibody (mAb3468, in green) that binds with sub‐nanomolar affinity (PDB ID: 1QFW). The structure illustrates the molecular complexity of the discontinuous and conformational β1/β3 binding site on hCGβ, and further suggests that the binding surfaces of hCGβ and mAb3468 only interact efficiently when they adopt the correct secondary and tertiary structures. On p. 91 ff. , P. Timmerman et al. present a new synthetic methodology for manufacturing small (3.5–5 kDa), peptide‐based mimics of the highly discontinuous β1/β3 epitope on hCGβ that retain both the secondary and tertiary structures as well as the strong binding to mAb3468, while neglecting 75 % of the total protein. Synthesis of these mimics involves the use of multiple constraints, including cyclization with a synthetic scaffold and connecting the loops both via oxime linkages and natural disulfide bonds. These constraints were shown to be essential for the binding properties of these mimics.