Position and orientation of gallated proanthocyanidins in lipid bilayer membranes: influence of polymerization degree and linkage type

Abstract

It is well known that the biological activity of gallated proanthocyanidins (PAs) is highly structure-dependent. Polymerization degree (DP) and linkage types affect their biological activity greatly. Positions and orientations of gallated PAs in lipid bilayer reveal their structure-function activity at the molecular level. The present work aimed at determining the locations and orientations of epigallocatechin-3-gallate (EGCG) and its derivatives: A-type and B-type EGCG dimers and trimers in 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl phosphatidylethanolamine (POPE) lipid bilayer via molecular dynamic (MD) simulations. The results showed that EGCG and its derivatives localized in the lipid bilayer or on the bilayer/water interface. Their penetration depths and orientations depended on both DP and linkage types. The penetration depths decreased with the increase of DP, sequencing to be EGCG > EGCG dimers > EGCG trimers. Spatially stretched A-type PAs could form more hydrogen bonds (H-bonds) with deep oxygen atoms of lipid bilayer and have higher affinity to the lipid bilayer than B-type PAs. Our results will provide an explicit evidence for PAs’ distinct biological activities.

Keywords:

• gallated proanthocyanidins
• polymerization degree
• linkage type
• molecular dynamic simulation
• lipid bilayer

Abbreviations:

• Epigallocatechin-3-gallate-(4β→8, 2β→O→7)-epigallocatechin-3-gallate, A-type EGCG dimer
• Epigallocatechin-3-gallate-(4β→8, 2β→O→7)-epigallocatechin-3-gallate-(4β→8, 2β→O→7)-epigallocatechin-3-gallate, A-type EGCG trimer
• Epigallocatechin-3-gallate-(4β→8)-epigallocatechin-3-gallate, B-type EGCG dimer
• Epigallocatechin-3-gallate-(4β→8)-epigallocatechin-3-gallate-(4β→8)-epigallocatechin-3-gallate, B-type EGCG trimer
• Center of Mass, COM
• Degree of Polymerization, DP
• Epigallocatechin-3-gallate, EGCG
• Molecular dynamics, MD
• 1-palmitoyl-2-oleoyl phosphatidylcholine, POPC
• 1-palmitoyl-2-oleoyl phosphatidylethanolamine, POPE
• Proanthocyanidins, PAs