Formation of high axial ratio microstructures from peptides modified with glutamic acid dialkyl amides

Abstract

A growing number of amphiphiles are known to form high axial ratio microstructures (HARMs) such as the hollow cylindrical microstructures called lipid tubules. As a prelude to exploring the potential of HARMs formed from lipopeptides in controlled release drug delivery, several microstructure formation conditions were investigated. We report the preparation of several glutamic acid dialkyl amides with varying alkyl chain lengths bearing a verity of peptides (1-4 amino acids) [peptide-Glu-(NHCnH2n+1)2, n=12, 14, 16]. These surfactants have been rapidly and efficiently converted into HARMs in aqueous buffer at physiological pH and ionic strength, or in buffer containing MeOH or EtOH. Helical ribbons and tubular HARMs were produced that were stable for as long as 6 months below the phase transition temperatures of the compounds. To estimate the stability of HARMs in vivo, HARMs formed from (Pro)3-Glu(NHC16H33)2 were incubated with DOPC liposomes or fetal calf serum at 40 degreesC. HARM size and shape did not change significantly, suggesting that such lipopeptide particles can retain their morphology long enough in vivo to be useful as drug delivery vehicles.

Structure and function of integral membrane protein domains resolved by peptide‐amphiphiles: Application to phospholamban

“…1 The number and length of tails, tail functional groups, and peptide sequence are all variable due to the modular design of peptide-amphiphiles. Lipidated peptides under the names of "peptide-amphiphiles," "lipopeptide conjugates," or "lipopeptides" have been developed for biomaterials functionalization, 2,3 for drug delivery systems, 4 for cell receptor mimetics, 3,5 for biosensors, 6 as a tool for probing signal transduction, 7 and for enhancement antimicrobial peptide activity. 8 Peptide-amphiphiles self-assemble into micelles and bilayer aggregates in aqueous solution, 9 placing the peptide headgroup into an environment similar to that experienced by the cytoplasmic or extracellular portion of a transmembrane protein.…”

Lipoproteins as drug delivery vehicles for cancer and tumor therapeutics

“…More specifically, lipopeptide particles coupled in vivo are proved more useful as drug delivery vehicles. 57 Liposome-based formulations are also prepared by using acetylated-LDL (Ac-LDL) as delivery vehicles for BPD (Table 4). 58…”

Chiral Molecular Self‐Assembly

“…76 Lee et al reported similar results on several glutamic acid dialkyl amides with short peptides in their head group. 77 Long fibers were found to rapidly form by thermal cycling of the compounds in either aqueous buffer or buffer containing methanol or ethanol. In particular, the proline derivative (Pro) 3 -Glu(NHC 12 H 25 ) 2 (25) formed helical ribbons similar to those observed by Shimizu and Hato.…”

“…76 However, slow cooling through T m , unlike incubation at room temperature, was found to cause direct self-assembly resulting in more stable helical morphologies. 77 A related system with the alkyl chains connected to the α-carboxylate and α-amino group of the amino acid was studied by Cescato et al 78 This left the side groups free for further functionalization. Aqueous dispersion of such amphiphiles with either glutamic acid (26) or arginine (27) residues formed spherically vesicles above T m .…”