Stereodivergent synthesis of 5-aminopipecolic acids and application in the preparation of a cyclic RGD peptidomimetic as a nanomolar αVβ3 integrin ligand†,Organic & Biomolecular Chemistry

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Stereodivergent synthesis of 5-aminopipecolic acids and application in the preparation of a cyclic RGD peptidomimetic as a nanomolar αVβ3 integrin ligand†
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2018-04-11 00:00:00 , DOI: 10.1039/c8ob00534f
Lorenzo Sernissi _{1,

2,

3,

4} , Luciano Ricci _{1,

2,

3,

4} , Dina Scarpi _{1,

2,

3,

4} , Francesca Bianchini _{4,

5,

6,

7,

8} , Daniela Arosio _{4,

9,

10,

11} , Alessandro Contini _{4,

12,

13,

14} , Ernesto G. Occhiato _{1,

2,

3,

4}

Affiliation

A stereodivergent strategy was devised to obtain enantiopure cis and trans 5-aminopipecolic acids (5-APAs) in suitably protected forms to be employed in peptide synthesis as conformationally constrained α- and δ-amino acids. The cis isomer was used as a δ-amino acid to construct a cyclic RGD-containing peptidomimetic, the ability of which to compete with biotinylated vitronectin for binding with the isolated α_Vβ₃ integrin was measured (IC₅₀ = 4.2 ± 0.9 nM). A complete ¹H NMR and computational conformational analysis was performed to elucidate the reasons for the high affinity of this cyclic peptidomimetic in comparison with cilengitide.

中文翻译：

5- aminopipecolic酸Stereodivergent合成和制备的环状RGD肽模拟物作为纳摩尔α应用_V β ₃整联蛋白配†

设计了立体发散策略，以得到适当保护形式的对映纯顺式和反式5-氨基哌酸（5-APA），以构象约束的α-和δ-氨基酸形式用于肽合成。的顺式异构体被用作δ氨基酸，构建环状含RGD的肽模拟物，其中，以与生物素化的玻连蛋白竞争与所述分离α结合的能力_V β ₃（IC整合测定₅₀ = 4.2±0.9 nm）的。进行了完整的¹ H NMR和计算构象分析，以阐明与cilengitide相比，该环状拟肽具有高亲和力的原因。

更新日期：2018-04-11

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