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US 5,604,203 AGranted
Analogs of peptide YY and uses thereof
AssigneeUniversity of Cincinnati
InventorAmbikaipakan Balasubramaniam
Life of this patent
Estimating the term…
Abstract
The invention provides analogs of PYY. The invention also provides compositions and methods useful for controlling biological activities such as cell proliferation, nutrient transport, lipolysis, and intestinal water and electrolyte secretion.
Claims29
A compound having the formula:
- ##STR3## wherein X is Cys or is deleted;
- each of R.sup.1 and R.sup.2 is bonded to the nitrogen atom of the .alpha.-amino group of the N-terminal amino acid;
- R.sub.1 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl;
- R.sub.2 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl;
- A.sup.22 is an aromatic amino acid, Ala, Aib, Anb, N-Me-Ala, or is deleted;
- A.sup.23 is Ser, Thr, Ala, Aib, N-Me-Ser, N-Me-Thr, N-Me-Ala, D-Trp, or is deleted;
- A.sup.24 is Leu, Gly, Ile, Val, Trp, Nle, Nva, Aib, Anb, N-Me-Leu, or is deleted;
- A.sup.25 is Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or an aryl group), Orn, or is deleted;
- A.sup.26 is Ala, His, Thr, 3-Me-His, 1-Me-His, .beta.-pyrozolylalanine, N-Me-His, Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or an aryl group), Orn, or is deleted;
- A.sup.27 is Nal, Bip, Pcp, Tic, Trp, Bth, Thi, or Dip;
- A.sup.28 is Leu, Val, Trp, Nle, Nva, Aib, Anb, or N-Me-Leu;
- A.sup.29 is Asn, Ala, Gln, Gly, Trp, or N-Me-Asn;
- A.sup.30 is Leu, Ile, Val, Trp, Nle, Nva, Aib, Anb, or N-Me-Leu;
- A.sup.31 is Val, Leu, Ile, Trp, Nle, Nva, Aib, Anb, or N-Me-Val;
- A.sup.32 is Thr, Ser, N-Me-Ser, N-Me-Thr, or D-Trp;
- A.sup.33 is Cys, Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or C.sub.6 -C.sub.18 aryl group), or Orn;
- A.sup.34 is Cys, Gln, Asn, Ala, Gly, N-Me-Gin, Aib, or Anb;
- A.sup.35 is Cys, Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or C.sub.6 -C.sub.18 aryl group), or Orn;
- A.sup.36 is an aromatic amino acid, or Cys;
- R.sub.3 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl;
- R.sub.4 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl, or a pharmaceutically acceptable salt thereof.
18 more elements
A compound having the formula:
- ##STR4## wherein each of R.sup.1 and R.sup.2 is bonded to the nitrogen atom of the .alpha.-amino group of the N-terminal amino acid;
- R.sub.1 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl;
- R.sub.2 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl;
- A.sup.25 is Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or an aryl group), Orn, or is deleted;
- A.sup.26 is Ala, His, Thr, 3-Me-His, .beta.-pyrozolylalanine, N-Me-His, Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or an aryl group), or Orn;
- A.sup.27 is an aromatic amino acid;
- A.sup.28 is Leu, Val, Trp, Nle, Nva, Aib, Aib, Anb, or N-Me-Leu;
- A.sup.29 is Asn, Ala, Gln, Gly, Trp, or N-Me-Asn;
- A.sup.30 is Leu, Ile, Val, Trp, Nle, Nva, Aib, Anb, or N-Me-Leu;
- A.sup.31 is Val, Leu, Ile, Trp, Nle, Nva, Aib, Anb, or N-Me-Val;
- A.sup.32 is Thr, Ser, N-Me-Ser, N-Me-Thr, or D-Trp;
- A.sup.33 is Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or C.sub.6 -C.sub.18 aryl group), Cys, or Orn;
- A.sup.34 is Cys, Gln, Asn, Ala, Gly, N-Me-Gin, Aib, or Anb;
- A.sup.35 is Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or C.sub.6 -C.sub.18 aryl group), Cys, or Orn;
- A.sup.36 is an aromatic amino acid, or Cys;
- R.sub.3 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl;
- and
- R.sub.4 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl, or a pharmaceutically acceptable salt thereof.
15 more elements
A compound having the formula:
- ##STR5## wherein X is Cys or is deleted;
- R.sub.1 and R.sub.2 are bonded to the N-terminal amino acid;
- R.sub.1 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl;
- R.sub.2 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl;
- A.sup.22 is an aromatic amino acid or is deleted;
- A.sup.23 is Ser, Thr, Ala, Aib, N-Me-Ser, N-Me-Thr, N-Me-Ala, D-Trp, or is deleted;
- A.sup.24 is Leu, Gly, Ile, Val, Trp, Nle, Nva, Aib, Anb, N-Me-Leu, or is deleted;
- A.sup.25 is Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or an aryl group), Orn, or is deleted;
- A.sup.26 is Ala, His, Thr, 3-Me-His, 1-Me-His, .beta.-pyrozolylalanine, N-Me-His, Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or an aryl group), or Orn;
- A.sup.27 is an aromatic amino acid other than Tyr;
- A.sup.28 is Leu, Val, Trp, Nle, Nva, Aib, Anb, or N-Me-Leu;
- A.sup.29 is Asn, Ala, Gln, Gly, Trp, or N-Me-Asn;
- A.sup.30 is Leu, Ile, Val, Trp, Nle, Nva, Aib, Anb, or N-Me-Leu;
- A.sup.31 is Val, Leu, Ile, Trp, Nle, Nva, Aib, Anb, or N-Me-Val;
- A.sup.32 is Thr, Ser, N-Me-Ser, N-Me-Thr, or D-Trp;
- A.sup.33 is Cys, Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or C.sub.6 -C.sub.18 aryl group), or Orn;
- A.sup.34 is Cys, Gln, Asn, Ala, Gly, N-Me-Gin, Aib, or Anb;
- A.sup.35 is Cys, Arg, Lys, homo-Arg, diethyl-homo-Arg, Lys-.epsilon.-NH--R (where R is H, a branched or straight chain C.sub.1 -C.sub.10 alkyl group, or C.sub.6 -C.sub.18 aryl group), or Orn;
- A.sup.36 is an aromatic amino acid, or Cys;
- R.sub.3 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl;
- R.sub.4 is H, C.sub.1 -C.sub.12 alkyl, C.sub.6 -C.sub.18 aryl, C.sub.1 -C.sub.12 acyl, C.sub.7 -C.sub.18 aralkyl, or C.sub.7 -C.sub.18 alkaryl, or a pharmaceutically acceptable salt thereof.
18 more elements
Dependencies are inferred from the claim text.