Amino acids, conformationally membrane-binding peptides

As for polyelectrolytes, peptide binding to phospholipid membranes and surfaces is expected to decrease with decreasing peptide length as a result of the increased entropy penalty (per amino acid) on adsorption. For peptides displaying adsorption-induced conformational changes, there is also a decreased tendency to form ordered... 

Enfuvirtide is a synthetic 36 -amino -acid peptide fusion inhibitor that blocks entry into the cell (Figure 49-4). Enfuvirtide, binds to the gp41 subunit of the viral envelope glycoprotein, preventing the conformational changes required for the fusion of the viral and cellular membranes. It has no activity against HIV-2. Enfuvirtide must be administered by subcutaneous injection. Metabolism appears to be by proteolytic hydrolysis without involvement of the CYP450 system. Elimination half-life is 3.8 hours. 

Relaxation-related work on proteins and polypeptides makes typically use of H, and NMR. A couple of papers have dealt with measurements on in fluorine-labelled aminoacids incorporated into peptide stuctures. Shi and co-workers introduced, at some specific sites, an unnatural fluorine-containing aminoacid and a nitroxide spin-label into a multidomain protein known to exist in different conformations. Measurements of F PRE allowed to determine the conformation under different conditions. Suzuki et used another fluorine-containing amino acid, inserted into different parts of a membrane-active peptide, as a local dynamics probe. They measured F transverse relaxation to examine changes in the mobility in different regions of the peptide upon binding to a lipid bilayer. 

Enfuvirtide is a 36 amino acid synthetic peptide used for managing HTV treatment-experienced patients. It is in powder form and must be reconstituted with sterile water for subcutaneous administration. The adult dose is 90 mg bd. Absorption does not vary by site of injection (for example, thigh, arm, or abdomen) [211 ]. Enfuvirtide binds to HR 1, blocking a conformational change on gp41 required for the fusion of the lipid envelope of HIV to the cytoplasmic membrane of CD4 T lyi ho-cytes, thus preventing viral entry [212 q. 

An amphipathic helix is defined as a helix in which the distribution of amino acid residues forms opposing polar and nonpolar faces. It is an important structural unit included in proteins and peptides and is responsible for interaction with biological membranes to elicit their biological functions such as membrane fusion. Influenza virus hemagglutinin [1], fertilin [1], and meltrin-a [2] contain amphipathic fusion peptides, which are likely to adopt a helical conformation during the fusion reaction. To clarify the role of amphipathic peptides in membrane fusion reactions, we synthesized five types of amphipathic model peptides and examined their helix formation, membrane binding and membrane fusion activities. 

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