The C-and N-terminal residues of synthetic heptapeptide ion channels influence transport efficacy through phospholipid bilayers

Natasha Djedovič, Riccardo Ferdani, Egan Harder, Jolanta Pajewska, Robert Pajewski, Michelle E. Weber, Paul H. Schlesinger, George W. Gokel

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The synthetic peptide, R2N-COCH2OCH 2CO-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° amides, or 3° 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′ = OCH2CH3; 10, OR′ = OCH(CH 3)2; 11, OR′ = O(CH2)6CH 3; 12, OR′ = OCH2-c-C6H11; 13, OR′ = O(CH2)9CH3; 14, OR′ = O(CH2)17CH3; 15, NR′2 = N[(CH2)6CH3]2; 16, NHR′ = NH(CH2)9CH3; 17, NR′2 = N[(CH2)9CH3]2; 18, NHR′ = NH(CH2)17CH3; 19, NR′2 = N[(CH2)17CH3]2. 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 C18 anchored esters 10-14, n-heptyl ester 11 was most active. For the C18 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.

Original languageEnglish
Pages (from-to)291-305
Number of pages15
JournalNew Journal of Chemistry
Volume29
Issue number2
DOIs
StatePublished - Feb 2005

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