Design and synthesis of a short-chain bitistatin analogue for imaging thrombi and emboli

Bioconjugate Chemistry
Kwamena E BaidooJ E Romano

Abstract

Previously, we showed that labeled bitistatin analogues possessed excellent characteristics for imaging both deep-vein thrombosis and pulmonary embolism. We hypothesized that the N-terminal amino acid sequence of bitistatin, which is different from other disintegrins, likely interacts with the binding site of platelets to confer desirable properties to bitistatin for imaging. In this study, we present the design, synthesis, and initial biological testing of a short-chain analogue of the native 83-amino-acid bitistatin sequence. Our initial molecular modeling of the binding loop of bitistatin showed that the minimal sequence that represented the binding region was a cyclic 10 amino acid sequence cyclo[Cys-Arg-Ile-Ala-Arg-Gly-Asp-Trp-Asn-Cys(S)]. Systematic modeling of a truncated N-terminal sequence of bitistatin fused with the optimized binding region having a thioether sequence through a Gaba spacer ultimately yielded the 24-amino acid peptide, cyclo-[CH(2)CO-Arg-Ile-Ala-Arg-Gly-Asp-Trp-Asn-Cys(S-)]-Gaba-Gly-Asn-Glu-Ile-Leu-Glu-Gln-Gly-Glu-Asp-Ser-Asp-Ser-Lys-OH, 1. The peptide was then coupled to the hydrazino-nicotinic acid bifunctional chelating agent and the purified adduct labeled with (99m)Tc using tricine as a coligand....Continue Reading

References

Mar 29, 2002·Journal of Applied Toxicology : JAT·J K Miller, D E Lenz

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Citations

Jul 17, 2014·Circulation. Cardiovascular Imaging·Hans J de HaasValentin Fuster
May 20, 2006·Journal of Peptide Science : an Official Publication of the European Peptide Society·Kade D RobertsAndrew M Bray
Jun 14, 2017·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·Gregory M LanzaXiaoxia Yang

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