Formation of Stable Vesicles fromN- or 3-Alkylindoles:  Possible Evidence for Tryptophan as a Membrane Anchor in Proteins

Abstract

Twelve indole derivatives have been prepared and studied. Five were 1-substituted: 1, methyl; 2, n-hexyl; 3, n-octyl; 4, n-octadecyl; and 5, cholestanyloxycarbonylmethyl. Four were 3-substituted: 6, methyl; 7, n-hexyl; 8, n-octyl; and 9, n-octadecyl. Three were disubstituted as follows: 10, 1-n-decyl-3- n-decyl; 11, 1-methyl-3-n-decyl; and 12, 1,3-bis(n-octadecyl)indole. Sonication of aqueous suspensions afforded stable aggregates from 3-5 and 8-12. Laser light scattering, dye entrapment, and electron microscopy were used to characterize the aggregates. Aggregates formed from N-substituted indoles proved to be more robust than those formed from 3-alkylindoles. A stable monolayer formed from 3-n-octadecylindole but not from N- or 1,3-disubstituted analogues by using a Langmuir-Blodgett trough. The formation of aggregates was explained in terms of stacking by the relatively polar indole headgroup. In the monolayer experiment, this force was apparently overwhelmed by H-bonding interactions with the aqueous phase.

Synthesis and antimicrobial activity of dermaseptin S1 analogues

“…A key factor is probably the steric encumbrance of the side chain, since Trp is believed to be a very good anchor point in the membrane. 20,21 In an attempt to improve the potency of DS1(1-15)-NH 2 we added a Lys residue to the N-terminus. Recent findings indicated that acylation of dermaseptin S4 fragments with long chain fatty acids, with or without an amino function in their structures, is well tolerated in terms of antimicrobial activity and is instrumental in modulating the potency and spectrum of activity in different assay conditions.…”

Cowpox Virus Protein CPXV012 Eludes CTLs by Blocking ATP Binding to TAP

“…Therefore, substitution of tryptophan may severely affect the insertion capacity of TM peptides. In many TM domains, including the active domain of the TAP inhibitor ICP47, tryptophan residues are located at the interfacial region, where they serve as a membrane anchor (40,(44)(45)(46)(47).…”

Coordination and transport of alkali metal cations through phospholipid bilayer membranes by hydraphile channels

“…An examination of the KcsA voltage gated potassium channel from Streptomyces lividans suggests that the indole residues of all the tryptophans in the structure occur at the insulator-midpolar boundary [45]. Tryptophan is the rarest of the 20 common amino acids and appears to play an important role as a stabilizing element [46][47][48] (Fig. 6).…”