New cyclic RGD peptide-anticancer agent conjugates, with different chemical functionalities attached to the parent peptide were synthesized in order to evaluate their biological activities and to provide a comparative study of their drug release profiles. The Integrin binding c(RGDfK) penta-peptide was used for the synthesis of Camptothecin (CPT) carbamate and Chlorambucil (CLB) amide conjugates. Substitution of the amino acid Lys with Ser resulted in a modified c(RGDfS) with a new attachment site, which enabled the synthesis of an ester CLB conjugate. Functional versatility of the conjugates was reflected in the variability of their drug release profiles, while the conserved RGD sequence of a selective binding to the αv integrin family, likely preserved their recognition by the Integrin and consequently their favorable toxicity towards targeted cancer cells. This hypothesis was supported by a computational analysis suggesting that all conjugates occupy conformational spaces similar to that of the Integrin bound bio-active parent peptide.
|Number of pages||10|
|Journal||Bioorganic and Medicinal Chemistry|
|State||Published - 15 Jan 2016|
Bibliographical noteFunding Information:
The authors thank Mrs. Cherna Moskowitz for generous stipend to Y.G. Financial support was provided by Ariel University Internal Research and Development Program .
© 2015 Elsevier Ltd. All rights reserved.
- Drug release profiles
- Molecular dynamics
- Targeted drug delivery