Djedovič Natasha, Ferdani Riccardo, Harder Egan, Pajewska Jolanta, Pajewski Robert, Weber Michelle E, Schlesinger Paul H, Gokel George W
Department of Molecular Biology & Pharmacology, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8103, St. Louis, MO 63110 U. S. A.
New J Chem. 2005 Jan 1;29(2):291-305. doi: 10.1039/b417091c.
The synthetic peptide, R(2)N-COCH(2)OCH(2)CO-Gly-Gly-Gly-Pro-Gly-Gly-Gly-OR', was shown to be selective for Cl(-) over K(+) when R is n-octadecyl and R' is benzyl. Nineteen heptapeptides have now been prepared in which the N-terminal and C-terminal residues have been varied. All of the N-terminal residues are dialkyl but the C-terminal chains are esters, 2 degrees amides, or 3 degrees amides. The compounds having varied N-terminal anchors and C-terminal benzyl groups are as follows: 1, R = n-propyl; 2, R = n-hexyl; 3, R = n-octyl; 4, R = n-decyl; 5, R = n-dodecyl; 6, R = n-tetradecyl; 7, R = n-hexadecyl; 8, R = n-octadecyl. Compounds 9-19 have R = n-octadecyl and C-terminal residues as follows: 9, OR' = OCH(2)CH(3); 10, OR' = OCH(CH(3))(2); 11, OR' = O(CH(2))(6)CH(3); 12, OR' = OCH(2)-c-C(6)H(11); 13, OR' = O(CH(2))(9)CH(3); 14, OR' = O (CH(2))(17)CH(3); 15, NR'(2) = N(CH(2))(6)CH(3); 16, NHR' = NH(CH(2))(9)CH(3); 17, NR'(2) = N(CH(2))(9)CH(3); 18, NHR' = NH(CH(2))(17)CH(3); 19, NR'(2) = N(CH(2))(17)CH(3). The highest anion transport activities were observed as follows. For the benzyl esters whose N-terminal residues were varied, i.e.1-8, compound 3 was most active. For the C(18) anchored esters 10-14, n-heptyl ester 11 was most active. For the C(18) anchored, C-terminal amides 15-19, di-n-decylamide 17 was most active. It was concluded that both the C- and N-terminal anchors were important for channel function in the bilayer but that activity was lost unless only one of the two anchoring groups was dominant.
当R为正十八烷基且R'为苄基时，合成肽R(2)N-COCH(2)OCH(2)CO-Gly-Gly-Gly-Pro-Gly-Gly-Gly-OR'对Cl(-)的选择性高于K(+)。现已制备了19种七肽，其中N端和C端残基有所变化。所有N端残基均为二烷基，但C端链为酯、仲酰胺或叔酰胺。具有不同N端锚定基团和C端苄基的化合物如下：1，R = 正丙基；2，R = 正己基；3，R = 正辛基；4，R = 正癸基；5，R = 正十二烷基；6，R = 正十四烷基；7，R = 正十六烷基；8，R = 正十八烷基。化合物9 - 19的R = 正十八烷基，C端残基如下：9，OR' = OCH(2)CH(3)；10，OR' = OCH(CH(3))(2)；11，OR' = O(CH(2))(6)CH(3)；12，OR' = OCH(2)-c-C(6)H(11)；13，OR' = O(CH(2))(9)CH(3)；14，OR' = O (CH(2))(17)CH(3)；15，NR'(2) = N(CH(2))(6)CH(3)；16，NHR' = NH(CH(2))(9)CH(3)；17，NR'(2) = N(CH(2))(9)CH(3)；18，NHR' = NH(CH(2))(17)CH(3)；19，NR'(2) = N(CH(2))(17)CH(3)。观察到的最高阴离子转运活性如下。对于N端残基不同的苄酯，即1 - 8，化合物3活性最高。对于C(18)锚定的酯10 - 14，正庚酯11活性最高。对于C(18)锚定的C端酰胺15 - 19，二正癸酰胺17活性最高。得出的结论是，C端和N端锚定基团对双层中的通道功能都很重要，但除非两个锚定基团中只有一个占主导，否则活性会丧失。
