Torrini I, Zecchini G P, Paradisi M P, Lucente G, Gavuzzo E, Mazza F, Pochetti G, Traniello S, Spisani S
Dipartimento di Studi Farmaceutici, Chimica del Farmaco del CNR Università La Sapienza, Roma, Italy.
Biopolymers. 1995 Apr;35(4):347-58. doi: 10.1002/bip.360350402.
As a continuation of the studies on chemotactic N-formylpeptides, we report here the synthesis and activity of a new cyclic analogue of the prototypical ligand For-Met-Leu-Phe-OMe. The new compound For-Met-Lys-Phe-For-Met-Lys-Phe- (4) contains a 20-membered cyclic moiety made up of a dimeric -Lys-Phe- sequence in which For-Met is attached to each Lys alpha-NH2 and hence remains outside the ring. The conformation in the crystal of the cyclic precursor of 4, namely Boc-Lys-Phe-Boc-Lys-Phe- (2) and the activity of the structurally related linear analogue For-Met-Lys(Z)-Phe-OBzl (6), have also been examined. The new analogues 4 and 6 are active as chemoattractants, secretagogues, and superoxide anion generating agents, when tested on human neutrophils. The structure-activity relationship is discussed and related to that of a previously studied cyclic model.
作为对趋化性N-甲酰肽研究的延续，我们在此报告原型配体N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸甲酯（For-Met-Leu-Phe-OMe）一种新的环状类似物的合成及活性。新化合物N-甲酰甲硫氨酰-赖氨酸-苯丙氨酸-N-甲酰甲硫氨酰-赖氨酸-苯丙氨酸-（4）含有一个由二聚体-Lys-Phe-序列组成的20元环状部分，其中N-甲酰甲硫氨酸连接到每个赖氨酸的α-NH2上，因此位于环外。还研究了4的环状前体即Boc-Lys-Phe-Boc-Lys-Phe-（2）在晶体中的构象以及结构相关的线性类似物N-甲酰甲硫氨酰-赖氨酸（Z）-苯丙氨酸苄酯（6）的活性。当在人中性粒细胞上进行测试时，新类似物4和6作为趋化剂、促分泌剂和超氧阴离子生成剂具有活性。讨论了构效关系并将其与先前研究的环状模型的构效关系相关联。
