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Solid‐phase synthesis of tailed cyclic RGD peptides using glutamic acid: unexpected glutarimide formation
Author(s) -
Zhu Junmin,
Marchant Roger E.
Publication year - 2008
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.975
Subject(s) - linker , chemistry , cyclic peptide , peptide , steric effects , stereochemistry , residue (chemistry) , solid phase synthesis , oligopeptide , peptide sequence , amino acid , sequence (biology) , combinatorial chemistry , biochemistry , computer science , gene , operating system
Abstract To provide multiple conjugating sites on cyclic peptides for their increasing biomedical applications, a tailed cyclic RGD peptide, c[RGDfE(GGGKK‐NH 2 )] was designed with c(RGDfE) linked through Glu to a tail consisting of a spacer of three Gly residues and a linker of two Lys residues. The spacer is used to increase the mobility and binding ability of the c(RGDfE) ligand, and the linker is used to proved multiple active sites for conjugating other molecules or biomaterials. We found that the sequence of Glu(Gly)‐OAll leads to glutarimide formation, which disrupts the formation of cyclic RGD peptides. However, our results show that glutarimide formation is sequence dependent and can be inhibited by incorporating an amino acid like Lys(Boc) with steric hindrance from the protecting group. To prevent glutarimide formation, Ser( t Bu) was used to replace the glycine in the GGG spacer adjacent to the residue of Glu, and a tailed cyclic RGD peptide, c[RGDfE(SGGKK‐NH 2 )] was successfully obtained. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.