Single-stranded DNA can invade an existing DNA duplex to form a D-loop by displacing one parental strand and forming Watson-Crick base pairs to the other. The analogous process in the collagen triple helix represents an alternate method for the treatment of skin wounds, but it has not been observed. Single-stranded collagen peptides that invaded frayed collagen fibrils on opposite sides of a wound would, in effect, close the wound without the need for suturing. To develop this method, the ability of single-stranded peptides to invade the collagen triple helix will be assessed. A heterotrimeric, triple-helical collagen mimic templated by a cysteine knot will be constructed and added to a solution of single-stranded peptide consisting of tripeptide repeats known to form hyperstable triple helices. Binding of the single strands to the host will be assayed by fluorescence anisotropy and ultracentrifugation. To extend the effective reach of the single strands across a wound, multiple single-stranded peptides will be attached to the arms of a PAMAMdendrimer, and the ability of this multimeric structure to invade multiple collagen hosts will be assayed.
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|Hodges, Jonathan A; Raines, Ronald T (2006) Energetics of an n --> pi interaction that impacts protein structure. Org Lett 8:4695-7|
|Hodges, Jonathan A; Raines, Ronald T (2005) Stereoelectronic and steric effects in the collagen triple helix: toward a code for strand association. J Am Chem Soc 127:15923-32|
|Hodges, Jonathan A; Raines, Ronald T (2003) Stereoelectronic effects on collagen stability: the dichotomy of 4-fluoroproline diastereomers. J Am Chem Soc 125:9262-3|