Estenne-Bouhtou G, Kullander K, Karlsson M, Ebendal T, Hacksell U, Luthman K
Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Centre, Uppsala University, Sweden.
Int J Pept Protein Res. 1996 Oct;48(4):337-46. doi: 10.1111/j.1399-3011.1996.tb00850.x.
Nine low molecular weight nerve growth factor (NGF)-like peptides have been designed to mimic the putative receptor-binding epitope of NGF defined by two beta-hairpin loops. Eight different spacers were used as variable links between the beta-loop amino acid residues, which from mutagenesis experiments were found to play an important role in the biological activity of NGF. These spacers were amino acids, natural or non-natural, differing in length (5-13 A) and polarity. The peptides were synthesized via the Fmoc solid-phase peptide synthesis and purified by reversed-phase HPLC. Their primary sequences were analyzed by a combination of automated Edman degradation and mass spectrometry. The peptides were tested using two different biological assays, the fibre outgrowth from chick embryonic sympathetic ganglia and the PC12 cell differentiation assay. Weak antagonistic effects could be observed for some peptides.
已设计出九种低分子量神经生长因子（NGF）样肽，以模拟由两个β-发夹环定义的NGF假定受体结合表位。八种不同的间隔物用作β-环氨基酸残基之间的可变连接，通过诱变实验发现这些间隔物在NGF的生物活性中起重要作用。这些间隔物是氨基酸，天然或非天然的，长度（5-13埃）和极性不同。这些肽通过Fmoc固相肽合成法合成，并通过反相高效液相色谱法纯化。它们的一级序列通过自动Edman降解和质谱联用进行分析。使用两种不同的生物学测定法对这些肽进行了测试，即鸡胚交感神经节的纤维生长和PC12细胞分化测定法。某些肽可观察到微弱的拮抗作用。
