Biologically active fragments of glucagon-like insulinotropic peptide
First Claim
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1. A GLP- 1 fragment of the formula:
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space="preserve" listing-type="equation">R.sup.1 -Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-TrP-Leu-Val-X-Gly-Arg-R.sup.2 (SEQ ID NO;
1)wherein R1 is selected from the group consisting of;
a) H2 N-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser (SEQ ID NO;
7); and
,b) H2 N-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser (SEQ ID NO;
8);
X is selected from the group consisting of Lys and Arg;
and wherein R2 is selected from the group consisting of NH2, OH, Gly-NH2, and Gly-OH, with the proviso that when R1 is b) and R2 is Gly-NH2 or Gly-OH, X must be Arg.
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Abstract
N-terminal truncated forms of glucagon like insulinotropic peptide (GLP-1) and analogs thereof are provided. The claimed polypeptides promote glucose uptake by cells but do not stimulate insulin expression or secretion. The invention also provides methods for treating diabetes and pharmaceutical formulations comprising the claimed polypeptides.
203 Citations
22 Claims
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1. A GLP- 1 fragment of the formula:
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space="preserve" listing-type="equation">R.sup.1 -Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-TrP-Leu-Val-X-Gly-Arg-R.sup.2 (SEQ ID NO;
1)wherein R1 is selected from the group consisting of; a) H2 N-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser (SEQ ID NO;
7); and
,b) H2 N-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser (SEQ ID NO;
8);X is selected from the group consisting of Lys and Arg; and wherein R2 is selected from the group consisting of NH2, OH, Gly-NH2, and Gly-OH, with the proviso that when R1 is b) and R2 is Gly-NH2 or Gly-OH, X must be Arg. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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21. A method of treating diabetes in a mammal comprising administering to a mammal in need of such treatment an effective amount of a GLP-1 fragment having the amino acid sequence:
- ##STR1##
- View Dependent Claims (22)
Specification