Recent advances in our understanding of protein conformational stability from a pharmaceutical perspective.
The marginal conformational stability of proteins has made them in some cases less than ideal candidates for pharmaceutical agents. Recent progress in our understanding of protein structure and stability has provided the opportunity to design the desired degree of stability into protein drug candidates. Modifications such as the optimisation of interior side-chain packing, the introduction of new ion-pairs, as well as the design of stabilising disulfide bridges and ligand binding sites, all offer the opportunity to produce proteins with enhanced stability properties.
Middaugh
C R
CR
Department of Pharmaceutical Chemistry, University of Kansas, 2095 Constant Avenue, Lawrence, KS 66047, USA.
Edwards
K L
KL