Coiled-coils: stability, specificity, and drug delivery potential.
The coiled-coil is a ubiquitous protein folding and assembly motif made of alpha-helices wrapping around each other forming a supercoil. The sequences of coiled-coils are made of seven-residue repeats, called heptads, and thus are polymer-like. Due to its simplicity and regularity, the coiled-coil is the most extensively studied protein motif. In this review, results on coiled-coil stability and specificity from structural and biophysical studies are summarized. It is pointed out that the primary sequences of coiled-coils over specify the secondary structure but under specify the tertiary/quaternary structure. This leads to two unique features of coiled-coil structure: linkage between stability and specificity and decoupling of secondary and tertiary/quaternary structural specificity. This is followed by a discussion of the potential of coiled-coils as drug delivery vehicles, particularly the prospect in two-staged pretargeted delivery. Such potentials are intimately related to the unique structural features of coiled-coils. The aim of this review is to illustrate how knowledge on protein stability and specificity can be used in the de novo design of peptide-based drug delivery vehicles with well-defined structure and interaction features.
Yu
Y Bruce
YB
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA. ybyl@utah.edu
D000071183:Autophagy-Related Proteins; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D056827:Endosomal Sorting Complexes Required for Transport; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins / Q000008:administration & dosage / Q000737:chemistry*; D013816:Thermodynamics; D014157:Transcription Factors / Q000008:administration & dosage / Q000737:chemistry*; D000099177:Tsg101 Protein
D000071183:Autophagy-Related Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D014157:Transcription Factors; D000099177:Tsg101 Protein; C428743:Rb1cc1 protein, mouse