The interaction of cytochrome c with two copolymers:poly(isobutylene-alt-maleic acid) (PIMA) and poly(1-tetradecene-alt-maleic acid) (PTMA) was studied in this report to investigate the electrostatic and hydrophobic influence of the copolymers on the structure of cytochrome c at acidic conditions.UV-Vis

circular dichroism and intrinsic tryptophan fluorescence were measured to study the secondary structure

Soret structure and tryptophan environment of cytochrome c.Cytochrome c maintains its native-like structure at pH=2.9.After interacting with the alternating copolymers of maleic acid and alkene at pH=2.9

the α-helical structure of cytochrome c is basically unchangeable

whereas its tertiary structure is destroyed.On the other hand

at pH=2.1

cytochrome c unfolds to random coil

and the alternating copolymers can induce a structural transition to α-helical structure for the acid-denatured cytochrome c but cannot induce the tertiary structure.In acidic solutions with lower copolymer concentration

the influence of PIMA on cytochrome c structure is stronger than that of PTMA

but at higher PTMA concentrations PTMA can reach similar effect as PIMA.The reason may be that at the same copolymer weight concentration

PIMA carries more negative charges therefore has stronger electrostatic interaction with cytochrome c

and that PTMA forms stable particles with hydrophobic cores which may decrease its effective concentration and decrease the interaction with cytochrome c.Compared to small molecules

the polymeric structure provides a favorable microenvironment for the structural transition of protein at very low copolymer concentrations.