| Project/Area Number |
13672249
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Kobe Pharmaceutical University (2002)
Tohoku University (2001) |
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Principal Investigator |
KOBAYASHI Norihiko Kobe Pharmaceutical University, Bioanalytical Chemistry, Professor, 薬学部, 教授 (90205477)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | molecule-recognizing module / cyclodextrin / antibody / variable region / subgroup / complementarity-determining region / antibody-mimetic peptide / CD-CDR |
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| Research Abstract |
Antibodies are useful functional molecules not only as a key reagent in diagnostic regents but also as therapeutic agents. However, conventional antibodies have some limitations for their applicability due to their large molecular weight (ca. 150,000). In this study, we attempted to generate the modified cyclodextrins (termed "CD-CDR") having an antibody-mimetic peptide as a novel molecule-recognizing module.
First, we cloned the V_H- and V_L-genes of various mouse monoclonal antibodies against steroids (corticosteroids, bile acids, estradiol, and digoxin) to determine the amino acid sequence of comple-mentarity-determining regions (CDRs) of each antibody. Then, 11-deoxycortisol (11-DC) was selected as a model guest compound, and a CD-CDR was synthesized by substitution of a primary hydroxyl group of β-cyclodextrin with a synthetic peptide containing the amino acid sequence of V_H-CDR3 of the anti-11-DC antibody. It was shown that the affinity of this CD-CDR to 11-DC is approximately five times greater than that of β-cyclodextrin itself. We expect that novel CD-CDR species with a practically high affinity and/or specificity could be isolated from a CD-CDR library prepared by introducing degenerated peptides with random amino acid sequences.
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