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Chemical synthesis and evaluation of a backbone‐cyclized minimized 2‐helix Z‐domain
Author(s) -
Järver Peter,
Mikaelsson Cecilia,
Karlström Amelie Eriksson
Publication year - 2011
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1346
Subject(s) - antiparallel (mathematics) , helix (gastropod) , chemistry , helix bundle , peptide , small molecule , molecule , ligand (biochemistry) , stereochemistry , binding domain , protein structure , immunoglobulin domain , protein a , combinatorial chemistry , crystallography , binding site , biochemistry , receptor , biology , antibody , physics , ecology , organic chemistry , quantum mechanics , snail , magnetic field , immunology
Abstract The Z‐molecule is a small, engineered IgG‐binding affinity protein derived from the immunoglobulin‐binding domain B of Staphylococcus aureus protein A. The Z‐domain consists of 58 amino acids forming a well‐defined antiparallel three‐helix structure. Two of the three helices are involved in ligand binding, whereas the third helix provides structural support to the three‐helix bundle. The small size and the stable three‐helix structure are two attractive properties comprised in the Z‐domain, but a further reduction in size of the protein is valuable for several reasons. Reduction in size facilitates synthetic production of any protein‐based molecule, which is beneficial from an economical viewpoint. In addition, a smaller protein is easier to manipulate through chemical modifications. By omitting the third stabilizing helix from the Z‐domain and joining the N ‐ and C ‐termini by a native peptide bond, the affinity protein obtains the advantageous properties of a smaller scaffold and in addition becomes resistant to exoproteases. We here demonstrate the synthesis and evaluation of a novel cyclic two‐helix Z‐domain. The molecule has retained affinity for its target protein, is resistant to heat treatment, and lacks both N ‐ and C ‐termini. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.