Synthesis and investigation of a new cyclo (Nα-dipicolinoyl) pentapeptide of a breast and CNS cytotoxic activity and an ionophoric specificity

被引:90
作者
Abo-Ghalia, M [1 ]
Amr, A [1 ]
机构
[1] Natl Res Ctr, Dep Chem Tanning Mat & Prot, Cairo 12622, Egypt
关键词
cyclopeptides; 2,6-pyridinedicarboxlic acid; peptide coupling methods; cytotoxic agents; ionophores;
D O I
10.1007/s00726-003-0042-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A new acylated cyclopentapeptide namely, Cyclo-(N-alpha-dipicolinoyl)-bis-[L-Leu-DL-Nval]-L-Lys OMe (5) was suggested and synthesized. The structural conception of 5 was rationalized by analogy to the structural features of some known cyclodepsipeptides exemplified by the antibiotic and DNA intercalator actinomycin D (NSC: 3053), the ionophore and anti-HIV enniatin B (NSC: 692895) and the ionophore and antibiotic valinomycin (NSC: 630175). The cyclopeptide 5 was chemically synthesized, starting from its linear tetrapeptide ester precursor 2 by coupling L-lysine methyl ester to the prepared tetrapeptide acid 3 or hydrazide 4 via the mixed anhydride or azide method, respectively. A cytotoxic activity (cell killing) in both breast (NCF7) and CNS (SF-268) cell lines NCI, USA) was realized for 5, while less active cytotoxic profile was determined for 2. Moreover, we have recently reported general ionophoric and sensor characteristics particularly, for Pb (II) ions for both 5 and 2. Correlation between the cytotoxic activity and the ionophoric potency is a matter of future investigations.
引用
收藏
页码:283 / 289
页数:7
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