Abstract
The success of solid-phase peptide synthesis is often dependent upon solvation of the resin and the growing resin-bound peptide chain. We investigated the relationship between solvent properties and solvation of the resin and peptide-resin in order to obtain satisfactory coupling yields for the rapid solid-phase peptide synthesis, using butyloxycarbonyl-(Boc)-amino acid derivatives, of human-α-calcitonin gene-related peptide(8-37) (CGRP(8-37)). Solvation of (p-methylbenzhydrylamine)copoly(styrene-1% divinylbenzene (DVB) (resin) and resin covalently bound to the fully protected amino acid sequence of CGRP(8-37) (peptide-resin) was correlated to solvent Hildebrand solubility (6) and hydrogen-bonding (δh) parameters. Contour solvation plots of δh vs. δ revealed maximum solvation regions of resin and peptide-resin. Maximum resin solvation occurred with N-methylpyrrolidinone (NMP), NMP:dimethylsulfoxide (DMSO) (8:2) and DMSO. Inefficient solvation of the peptide-resin occurred with these solvents and resulted in poor syntheses with average coupling yields of 78.1, 88.9 and 91.8%, respectively. Superior peptide-resin solvation was obtained using dimethylacetamide (DMA) and dimethylformamide (DMF), resulting in significantly higher average coupling yields of 98.0 and 99.5%, respectively. Thus, the region of maximum peptide-resin solvation shifts to solvents with higher δh values. DMF provided the most effective peptide-resin solvation and was the only solvent from which CGRP(8-37) was obtained as a single major product in the crude cleaved material.
| Original language | English |
|---|---|
| Pages (from-to) | 84-89 |
| Number of pages | 6 |
| Journal | Journal of Peptide Research |
| Volume | 65 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2005 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Endocrinology
Cite this
Solvent effects on coupling yields during rapid solid-phase synthesis of CGRP(8-37) employing in situ neutralization. / Taylor, C. K.; Abel, Peter W.; Hulce, Martin; Smith, D. D.
In: Journal of Peptide Research, Vol. 65, No. 1, 01.2005, p. 84-89.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Solvent effects on coupling yields during rapid solid-phase synthesis of CGRP(8-37) employing in situ neutralization
AU - Taylor, C. K.
AU - Abel, Peter W.
AU - Hulce, Martin
AU - Smith, D. D.
PY - 2005/1
Y1 - 2005/1
N2 - The success of solid-phase peptide synthesis is often dependent upon solvation of the resin and the growing resin-bound peptide chain. We investigated the relationship between solvent properties and solvation of the resin and peptide-resin in order to obtain satisfactory coupling yields for the rapid solid-phase peptide synthesis, using butyloxycarbonyl-(Boc)-amino acid derivatives, of human-α-calcitonin gene-related peptide(8-37) (CGRP(8-37)). Solvation of (p-methylbenzhydrylamine)copoly(styrene-1% divinylbenzene (DVB) (resin) and resin covalently bound to the fully protected amino acid sequence of CGRP(8-37) (peptide-resin) was correlated to solvent Hildebrand solubility (6) and hydrogen-bonding (δh) parameters. Contour solvation plots of δh vs. δ revealed maximum solvation regions of resin and peptide-resin. Maximum resin solvation occurred with N-methylpyrrolidinone (NMP), NMP:dimethylsulfoxide (DMSO) (8:2) and DMSO. Inefficient solvation of the peptide-resin occurred with these solvents and resulted in poor syntheses with average coupling yields of 78.1, 88.9 and 91.8%, respectively. Superior peptide-resin solvation was obtained using dimethylacetamide (DMA) and dimethylformamide (DMF), resulting in significantly higher average coupling yields of 98.0 and 99.5%, respectively. Thus, the region of maximum peptide-resin solvation shifts to solvents with higher δh values. DMF provided the most effective peptide-resin solvation and was the only solvent from which CGRP(8-37) was obtained as a single major product in the crude cleaved material.
AB - The success of solid-phase peptide synthesis is often dependent upon solvation of the resin and the growing resin-bound peptide chain. We investigated the relationship between solvent properties and solvation of the resin and peptide-resin in order to obtain satisfactory coupling yields for the rapid solid-phase peptide synthesis, using butyloxycarbonyl-(Boc)-amino acid derivatives, of human-α-calcitonin gene-related peptide(8-37) (CGRP(8-37)). Solvation of (p-methylbenzhydrylamine)copoly(styrene-1% divinylbenzene (DVB) (resin) and resin covalently bound to the fully protected amino acid sequence of CGRP(8-37) (peptide-resin) was correlated to solvent Hildebrand solubility (6) and hydrogen-bonding (δh) parameters. Contour solvation plots of δh vs. δ revealed maximum solvation regions of resin and peptide-resin. Maximum resin solvation occurred with N-methylpyrrolidinone (NMP), NMP:dimethylsulfoxide (DMSO) (8:2) and DMSO. Inefficient solvation of the peptide-resin occurred with these solvents and resulted in poor syntheses with average coupling yields of 78.1, 88.9 and 91.8%, respectively. Superior peptide-resin solvation was obtained using dimethylacetamide (DMA) and dimethylformamide (DMF), resulting in significantly higher average coupling yields of 98.0 and 99.5%, respectively. Thus, the region of maximum peptide-resin solvation shifts to solvents with higher δh values. DMF provided the most effective peptide-resin solvation and was the only solvent from which CGRP(8-37) was obtained as a single major product in the crude cleaved material.
UR - http://www.scopus.com/inward/record.url?scp=14044249460&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14044249460&partnerID=8YFLogxK
U2 - 10.1111/j.1399-3011.2004.00200.x
DO - 10.1111/j.1399-3011.2004.00200.x
M3 - Article
C2 - 15686538
AN - SCOPUS:14044249460
VL - 65
SP - 84
EP - 89
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
SN - 1747-0277
IS - 1
ER -