Pagani Zecchini G, Paglialunga Paradisi M, Torrini I, Lucente G, Mastropietro G, Paci M, Spisani S
Dipartimento di Studi Farmaceutici, Università La Sapienza, Roma, Italy.
Arch Pharm (Weinheim). 1996 Dec;329(12):517-23. doi: 10.1002/ardp.19963291202.
The role exercised by the central residue of the chemotactic N-formyltripeptide HCO-Met-Leu-Phe-OMe (fMLP-OMe) in controlling both the backbone conformation and the biochemical activity is the subject of recent interest. Here, two new centrally constrained fMLP-OMe analogues, namely HCO-Met-azaPro-Phe-OMe (4) and HCO-Met-(gamma-lactam)-Phe-OMe (6) have been synthesized and their CDCI3 solution conformation and activity have been studied. The azapeptide 4 adopts beta-folded conformation with the azaPro residue at the i+2 position and an intramolecular H-bond involving the formylic oxygen and the Phe NH. The gamma-lactam tripeptide 6 prefers a semi-extended backbone conformation. When tested on human neutrophils both the new models were found practically devoid of biological activity. The role exerted by the NH groups as well as by the conformational preferences is discussed.
趋化性N-甲酰三肽HCO-Met-Leu-Phe-OMe（fMLP-OMe）的中心残基在控制主链构象和生化活性方面所起的作用是近期研究的热点。在此，合成了两种新的中心受限fMLP-OMe类似物，即HCO-Met-氮杂脯氨酸-Phe-OMe（4）和HCO-Met-（γ-内酰胺）-Phe-OMe（6），并研究了它们在CDCI3溶液中的构象和活性。氮杂肽4采用β折叠构象，氮杂脯氨酸残基位于i+2位置，且存在一个涉及甲酰基氧和苯丙氨酸NH的分子内氢键。γ-内酰胺三肽6更倾向于半伸展的主链构象。在对人中性粒细胞进行测试时，发现这两种新模型几乎都没有生物活性。讨论了NH基团以及构象偏好所起的作用。
