Lipopeptide conjugates: biomolecular building blocks for receptor activating membrane-mimetic structures.
A simple method for the derivatization of phospholipid subunits with short peptide sequences is presented. Amphiphilic conjugates of distearoylphosphatidylethanolamine (DSPE) and the minimal human thrombin-receptor peptide agonist SFLLRN were synthesized via coupling of the bromoacetyl derivative of DSPE (PEBr) with a thiol-terminated decapeptide of SFLLRN. Bromoderivatization of DSPE was performed by condensation of bromoacetic acid and DSPE, with an overall yield of 40%. Coupling of PEBr and the unprotected thiol-terminated decapeptide was performed in chloroform/methanol/water in the presence of triethylamine and afforded 25.5% of the lipopeptide. The compound was characterized by TLC, 1H-NMR (600 MHz) and mass spectrometry. Lipopeptide bioactivity was confirmed by a platelet aggregation assay. The EC50 of the all-L amino acid lipopeptide was 38 +/- 3 microM. The all-D conjugate was inactive. Model receptor-activating systems, including well-ordered assemblies of amphiphilic phospholipid-peptide conjugates, represent the first step in the construction of bioactive surfaces for tissue engineering based on a membrane-mimetic approach.
Winger
T M
TM
School of Chemical Engineering, Georgia Institute of Technology, Atlanta 30322, USA.
Ludovice
P J
PJ
Chaikof
E L
EL
D017605:Bromine Compounds / Q000138:chemical synthesis; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008074:Lipoproteins / Q000138:chemical synthesis* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000138:chemical synthesis / Q000494:pharmacology; D010743:Phospholipids / Q000138:chemical synthesis* / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D018179:Receptors, Thrombin / Q000819:agonists*; D013329:Structure-Activity Relationship
D017605:Bromine Compounds; D008074:Lipoproteins; D010446:Peptide Fragments; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); C038089:1,2-distearoylphosphatidylethanolamine