Abstract: Herewith, we report for the very first time the crystal structure of tetrapeptide FwKT (PheD-Trp-Lys-Thr), which is considered to represent an epitope for biomedically relevant hormone somatostatin. This peptide is interesting because all drugs based on somatostatin analogs have been developed on the basis of its pharmacophore sequence Phe-Trp-Lys-Thr which is responsible for their binding to somatostatin receptors (sstr), the overexpression of which is observed in tumor cells. The target molecule was successfully crystalized, solved and refined as a conjugate of the tetrapeptide moiety bearing a protective group DOTA (1,4,7,10-tetraazacyclododecane - 1,4,7,10-tetraacetic acid) at the N-terminus and methylated at the O-terminus. The combination of a hormone active site and a powerful chelator make the substance a highly prospective targeted drug delivery system.

Cite: Dyusenova S.E. , Arkhipov S.G. , Lazarenko V.A. , Avdeev D. , Khachatryan D.S. , Medvedev M. , Dorovatovskii P.V. , Nikolaeva A. , Ovchinnikov M. , Sidorova M. , Zubavichus Y.V.
The Crystal Structure Elucidation of a Tetrapeptide Analogue of Somatostatin DOTA-Phe-D-Trp-Lys-Thr-OMe
International Workshop on Chemical Crystallography and Structural Biology “The Third Struchkov Meeting” 15-19 Nov 2021