found by using two orthogonal cyclic pentapeptide libraries involving conformation-based and sequence-based libraries based on the pharmacophore of a 14-mer peptidic antagonist, 1. Herein, cyclic tetrapeptides derived from replacements of the dipeptide unit (Nal-Gly) with a gamma-amino acid and pseudopeptides cyclized by disulfide and olefin bridges were synthesized to find novel scaffold structures different
先前通过使用两个正交环状五肽文库发现了一种高效CXCR4拮抗剂化合物2,所述正交五环文库涉及基于14-mer肽拮抗剂1的药效基团的基于构象和基于序列的文库。合成了具有γ-
氨基酸的二肽单元(Nal-Gly)以及由二
硫键和烯烃桥环合的假肽,以发现不同于环状五肽的新型支架结构。与化合物2相比,这些化合物包含的肽键数量减少。此外,还制备了几种具有Arg(4)侧链
化学修饰的类似物(2)。由此,鉴定了具有高至中等CXCR4拮抗活性的几种新的
铅。