STABILIZATION OF VASOACTIVE-INTESTINAL-PEPTIDE BY LIPIDS

An anionic phospholipid, phosphatidylglycerol (PG), induced vasoactive intestinal peptide (VIP) to adopt a helical conformation, determined by circular dichroism studies. PG inhibited the trypsin-catalyzed, ant ibody-catalyzed and uncatalyzed cleavage of VIP, measured by radiometr ic and HPLC methods. Phosphatidylcholine, a neutral lipid, did not alt er the circular dichroism spectra of VIP, and it was without detectabl e effect on the rates of VIP cleavage. Trypsin-catalyzed cleavage of B oc-Ile-Glu-Arg-methylcoumarinamide, a substrate unrelated in sequence to VIP, proceeded at equivalent rates in the absence and presence of P G, which suggests that the phospholipid did not exert a nonspecific in hibitory effect on the enzyme. Study of the kinetics of antibody-catal yzed VIP cleavage indicated that the inhibition by PG was due to decre ased affinity for VIP, suggested by observations of increased K-m valu es and unaltered V-max values. Incorporation of VIP in the liposomes a nd the liposomal surface permitted maintenance of the peptide in essen tially undegraded form at 37 degrees C for 8 days. The longevity of li posomal VIP administered i.v. to mice was increased by about 5-fold co mpared with aqueous VIP. These observations indicate that certain phos pholipids and liposomes can be applied to circumvent the rapid loss of VIP in vitro and in vivo due to degradative processes.