title: Effects of solute-solute interactions on protein stability studied using various counterions and dendrimers.
abstract: Much work has been performed on understanding the effects of additives on protein thermodynamics and degradation kinetics, in particular addressing the Hofmeister series and other broad empirical phenomena. Little attention, however, has been paid to the effect of additive-additive interactions on proteins. Our group and others have recently shown that such interactions can actually govern protein events, such as aggregation. Here we use dendrimers, which have the advantage that both size and surface chemical groups can be changed and therein studied independently. Dendrimers are a relatively new and broad class of materials which have been demonstrated useful in biological and therapeutic applications, such as drug delivery, perturbing amyloid formation, etc. Guanidinium modified dendrimers pose an interesting case given that guanidinium can form multiple attractive hydrogen bonds with either a protein surface or other components in solution, such as hydrogen bond accepting counterions. Here we present a study which shows that the behavior of such macromolecule species (modified PAMAM dendrimers) is governed by intra-solvent interactions. Attractive guanidinium-anion interactions seem to cause clustering in solution, which inhibits cooperative binding to the protein surface but at the same time, significantly suppresses nonnative aggregation.
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors: Curtiss P
authors: CP
authors: Schneider
authors: Diwakar
authors: D
authors: Shukla
authors: Bernhardt L
authors: BL
authors: Trout
mesh_terms: D000818:Animals; D000838:Anions / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D032449:Canavalia / Q000737:chemistry; D002417:Cattle; D002919:Chymotrypsinogen / Q000737:chemistry; D003208:Concanavalin A / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D019791:Guanidine / Q000737:chemistry; D007477:Ions / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000838:Anions; D050091:Dendrimers; D007477:Ions; C104700:PAMAM Starburst; D011506:Proteins; D012996:Solutions; D003208:Concanavalin A; D002919:Chymotrypsinogen; D019791:Guanidine