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result sql = Synthesis and evaluation of keto-glutamine analogues as inhibitors of hepatitis A virus 3C proteinase.
Synthesis and evaluation of keto-glutamine analogues as inhibitors of hepatitis A virus 3C proteinase.
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char = f;code = 102
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = g;code = 103
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char = n;code = 110
char = ;code = 32
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char = o;code = 111
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = t;code = 116
char = o;code = 111
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char = e;code = 101
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char = t;code = 116
char = o;code = 111
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char = n;code = 110
char = ;code = 32
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char = d;code = 100
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char = i;code = 105
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char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = t;code = 116
char = e;code = 101
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char = r;code = 114
char = a;code = 97
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char = e;code = 101
char = p;code = 112
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char = i;code = 105
char = d;code = 100
char = e;code = 101
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char = p;code = 112
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char = t;code = 116
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char = h;code = 104
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char = d;code = 100
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char = ;code = 32
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char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
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char = ;code = 32
char = a;code = 97
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char = m;code = 109
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char = t;code = 116
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char = e;code = 101
char = ;code = 32
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char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
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char = b;code = 98
char = l;code = 108
char = e;code = 101
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char = i;code = 105
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char = i;code = 105
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char = i;code = 105
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char = (;code = 40
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char = );code = 41
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char = n;code = 110
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char = ;code = 32
char = a;code = 97
char = l;code = 108
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char = o;code = 111
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
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char = n;code = 110
char = c;code = 99
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char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = e;code = 101
char = i;code = 105
char = t;code = 116
char = o;code = 111
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char = /;code = 47
char = >;code = 62
result sql = Hepatitis A virus (HAV) 3C enzyme is a picornaviral cysteine proteinase involved in the processing of the initially synthesized viral polyprotein and is therefore important for viral maturation and infectivity. Although it is a cysteine proteinase, this enzyme has a topology similar to those of the chymotrypsin-like serine proteinases. Since the enzyme recognizes peptide substrates with a glutamine residue at the P(1) site, a number of ketone-containing glutamine compounds analogous to nanomolar inhibitors of cathepsin K were synthesized and tested for inhibition against HAV 3C proteinase. In addition, a 3-azetidinone scaffold was incorporated into the glutamine fragment but gave only modest inhibition. However, introduction of a phthalhydrazido group alpha to the ketone moiety gave significantly better inhibitors with IC(50) values ranging from 13 to 164 microM, presumably due to the effect of intramolecular hydrogen bonding to the ketone. In addition, the tetrapeptide phthalhydrazide 24 was found to be a competitive reversible inhibitor (K(i) = 9 x 10(-6) M) and also showed no loss of inhibitory potency in the presence of dithiothreitol.

Publication: J. Org. Chem. 2002 May 17 ;67(10)::3169-78.
Publication Date: 2002 May 17
Study Author(s): Ramtohul, Yeeman K;James, Michael N G;Vederas, John C;
Institution: Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
Shortcut link to this study:
Hepatitis A virus (HAV) 3C enzyme is a picornaviral cysteine proteinase involved in the processing of the initially synthesized viral polyprotein and is therefore important for viral maturation and infectivity. Although it is a cysteine proteinase, this enzyme has a topology similar to those of the chymotrypsin-like serine proteinases. Since the enzyme recognizes peptide substrates with a glutamine residue at the P(1) site, a number of ketone-containing glutamine compounds analogous to nanomolar inhibitors of cathepsin K were synthesized and tested for inhibition against HAV 3C proteinase. In addition, a 3-azetidinone scaffold was incorporated into the glutamine fragment but gave only modest inhibition. However, introduction of a phthalhydrazido group alpha to the ketone moiety gave significantly better inhibitors with IC(50) values ranging from 13 to 164 microM, presumably due to the effect of intramolecular hydrogen bonding to the ketone. In addition, the tetrapeptide phthalhydrazide 24 was found to be a competitive reversible inhibitor (K(i) = 9 x 10(-6) M) and also showed no loss of inhibitory potency in the presence of dithiothreitol.
PMID: 12003522

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