The effect of modification on the susceptibility of collagen to proteolysis: I. Chemical modification of amino acid side chains.
A series of chemically modified collagens were subjected to proteolysis by lysozomal cathepsins, pepsin and trypsin. Modifications of the collagens included acetylation, succinylation, methylation and borohydride reduction. Changes in the integrity of the materials were also monitored by differential scanning calorimetry (DSC). All modified collagens were implanted intramuscularly to assess their relative biodegradation rates in vivo. Methylation of the collagen showed extensive denaturation as confirmed by DSC, pepsin solublization to small fragments and by increased susceptibility to trypsin. However, methylation and succinylation made little difference to hydrolysis by cathepsins. Acetylation and borohydride reduction gave increased resistance to cathepsins as well as to pepsin, this latter also being found with the succinylated substrate. In-vivo implantation data showed both succinylation and methylation increased the rate of biodegradation but that the other modifications did not affect the rate of breakdown when compared with control unmodified collagen. The results of this study showed that chemical modification of collagen can alter in vivo degradation rates and could aid in designing collagen-based prostheses.
Diamond
A M
AM
Johnson and Johnson Medical Biopolymer Group, Scottish Metropolitan Alpha Centre, Stirling University Innovation Park, UK.
Gorham
S D
SD
Etherington
D J
DJ
Robertson
J G
JG
Light
N D
ND
D000107:Acetylation; D000818:Animals; D001894:Borohydrides / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D002403:Cathepsins / Q000378:metabolism; D003094:Collagen / Q000031:analogs & derivatives / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008745:Methylation; D009132:Muscles / Q000378:metabolism; D010084:Oxidation-Reduction; D010434:Pepsin A / Q000378:metabolism; D011489:Protein Denaturation; D051381:Rats; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D014357:Trypsin / Q000378:metabolism
D001894:Borohydrides; D013386:Succinates; C025364:sodium borohydride; D003094:Collagen; D019802:Succinic Acid; D002403:Cathepsins; D014357:Trypsin; D010434:Pepsin A