IMPROVED PEPTIDE PHARMACEUTICALS

1 . A peptide product comprising a surfactant X, covalently attached to a GLP-1 receptor (GLP1R) and/or glucagon receptor (GCGR) binding peptide, the peptide product comprising:

wherein X is

wherein

A is a hydrophobic group comprising a C 1 -C 30 alkyl chain or an aralkyl chain; and

B is a hydrophilic saccharide group covalently attached to the peptide via a linker amino acid U, wherein U is a natural or unnatural amino acid.

2 . The peptide product of claim 1 , wherein the peptide binds GLP1R and GCGR.

3 . The peptide product of claim 1 , wherein A is a substituted or unsubstituted C 3 -C 20 alkyl chain.

4 . The peptide product of claim 1 , wherein the surfactant X is an N-linked alkyl glycoside comprising one or more hydroxyl functions modified to be a carboxylic acid.

5 . The peptide product of claim 1 , wherein the the surfactant X comprises a carboxylic acid group.

6 . The peptide product of claim 1 , wherein the saccharide is selected from glucose, mannose, maltose, a glucuronic acid, galacturonic acid, diglucuronic acid and maltouronic acid.

7 . The peptide product of claim 1 , wherein the surfactant is a 1-alkyl glycoside class surfactant.

8 . The peptide product of claim 1 , wherein the saccharide group is attached to the peptide via an amide bond.

9 . The peptide product of claim 1 , wherein the surfactant X is comprised of 1-eicosyl beta-D-glucuronic acid, 1-octadecyl beta-D-glucuronic acid, 1-hexadecyl beta-D-glucuronic acid, 1-tetradecylbeta D-glucuronic acid, 1-dodecyl beta D-glucuronic acid, 1-decyl beta-D-glucuronic acid, 1-octyl beta-D-glucuronic acid, 1-eicosyl beta-D-diglucuronic acid, 1-octadecyl beta-D-diglucuronic acid, 1-hexadecyl beta-D-diglucuronic acid, 1-tetradecyl beta-D-diglucuronic acid, 1-dodecyl beta-D-diglucuronic acid, 1-decyl beta-D-diglucuronic acid, 1-octyl beta-D-diglucuronic acid, or functionalized 1-ecosyl beta-D-glucose, 1-octadecyl beta-D-glucose, 1-hexadecyl beta-D-glucose, 1-tetradecyl beta-D-glucose, 1-dodecyl beta-D-glucose, 1-decyl beta-D-glucose, 1-octyl beta-D-glucose, 1-eicosyl beta-D-maltoside, 1-octadecyl beta-D-maltoside, 1-hexadecyl beta-D-maltoside, 1-dodecyl beta-D-maltoside, 1-decyl beta-D-maltoside, or 1-octyl beta-D-maltoside.

10 . The peptide product of claim 1 , wherein the peptide product comprises a covalently linked N-omega-1-alkyl β-D-glucuronyl.

11 . The peptide product of claim 1 , wherein the peptide comprises aa 1 to aa 26 of SEQ ID NO: 304;

aa 1 -aa 2 -aa 3 -aa 4 -aa 5 -aa 6 -aa 7 -aa 8 -aa 9 -aa 10 -aa 11 -aa 12 -aa 13 -aa 14 -aa 15 -aa 16 -aa 17 -aa 18 -aa 19 -aa 20 -aa 21 -aa 22 -aa 23 -aa 24 -aa 25 -aa 26 -aa 27 -aa 28 -aa 29 -Z (SEQ. ID. NO. 304)

wherein:

Z is OH, or —NH—R 3 , wherein R 3 is H, or C 1 -C 12 substituted or unsubstituted alkyl, or a PEG chain of less than 10 Da;

aa 1 is His, N—Ac-His, pGlu-His, or N—R 3 -His;

aa 2 is Ser, Ala, Gly, Aib, Ac4c, or Ac5c;

aa 3 is Gln, or Cit;

aa 4 is Gly, or D-Ala;

aa 5 is Thr, or Ser;

aa 6 is Phe, Trp, F2Phe, Me2Phe, or Nal2;

aa 7 is Thr, or Ser;

aa 8 is Ser, or Asp;

aa 9 is Asp, or Glu;

aa 10 is Tyr, Leu, Met, Nal2, Bip, or Bip2EtMeO;

aa 11 is Ser, Asn, or U;

aa 12 is Lys, Glu, Ser, Arg, or U(X);

aa 13 is absent or Tyr, Gln, Cit, or U(X);

aa 14 is absent or Leu, Met, Nle, or U(X);

aa 15 is absent or Asp, Glu, or U(X);

aa 16 is absent or Ser, Gly, Glu, Aib, Ac5c, Lys, Arg, or U(X);

aa 17 is absent or Arg, hArg, Gln, Glu, Cit, Aib, Ac4c, Ac5c, or U(X);

aa 18 is absent or Arg, hArg, Ala, Aib, Ac4c, Ac5c, or U(X);

aa 19 is absent or Ala, Val, Aib, Ac4c, Ac5c, or U(X);

aa 20 is absent or Gln, Lys, Arg, Cit, Glu, Aib, Ac4c, Ac5c, or U(X);

aa 21 is absent or Asp, Glu, Leu, Aib, Ac4c, Ac5c, or U(X);

aa 22 is absent or Phe, Trp, Nal2, Aib, Ac4c, Ac5c, or U(X);

aa 23 is absent or Val, Ile, Aib, Ac4c, Ac5c, or U(X);

aa 24 is absent or Gln, Ala, Glu, Cit, or U(X);

aa 25 is absent or Trp, Nal2, or U(X);

aa 26 is absent or Leu, or U(X);

aa 27 is absent;

aa 28 is absent;

aa 29 is absent;

wherein any two of aa 1 -aa 26 are optionally cyclized through their side chains to form a lactam linkage; and

provided that one, or at least one of aa 16 , aa 17 , aa 18 , aa 19 , aa 20 , aa 21 , aa 22 , aa 23 , aa 24 , or aa 25 is the linker amino acid U covalently attached to the surfactant X.

12 . The peptide product of claim 1 , wherein the peptide comprises SEQ ID NO: 305

(SEQ ID. NO. 305)

His 1 -aa 2 -aa 3 -Gly 4 -Thr 5 -aa 6 -Thr 7 -Ser 8 -Asp 9 -aa 10 -aa 11 -

aa 12 -aa 13 -aa 14 -aa 15 -aa 16 -aa 17 -aa 18 -aa 19 -aa 20 -aa 21 -aa 22 -

aa 23 -Z

wherein:

Z is OH, or —NH—R 3 , wherein R 3 is H or substituted or unsubstituted C 1 -C 12 alkyl; or a PEG chain of less than 10 Da;

aa 2 is Ser, Ala, Gly, Aib, Ac4c, or Ac5c;

aa 3 is Gln, or Cit;

aa 6 is Phe, Trp, F2Phe, Me2Phe, MePhe, or Nal2;

aa 10 is Tyr, Leu, Met, Nal2, Bip, or Bip2EtMeO;

aa 11 is Ser, Asn, or U(X);

aa 12 is Lys, Glu, Ser, or U(X);

aa 13 is absent or Tyr, Gln, Cit, or U(X);

aa 14 is absent or Leu, Met, Nle, or U(X);

aa 15 is absent or Asp, Glu, or U(X);

aa 16 is absent or Ser, Gly, Glu, Aib, Ac4c, Ac5c, Lys, R, or U(X);

aa 17 is absent or Arg, hArg, Gln, Glu, Cit, Aib, Ac4c, Ac5c, or U(X);

aa 18 is absent or Arg, hArg, Ala, Aib, Ac4c, Ac5c, or U(X);

aa 19 is absent or Ala, Val, Aib, Ac4c, Ac5c, or U(X);

aa 20 is absent or Gln, Lys, Arg, Cit, Glu, Aib, Ac4c, Ac5c, or U(X);

aa 21 is absent or Asp, Glu, Leu, Aib, Ac4c, Ac5c, or U(X);

aa 22 is absent or Phe, Aib, Ac4c, Ac5c, or U(X)

aa 23 is absent or Val, Ile, Aib, Ac4c, Ac5c, or U(X);

wherein any two of aa 1 -aa 23 are optionally cyclized through their side chains to form a lactam linkage; and

provided that one, or at least one of aa 16 , aa 17 , aa 18 , aa 19 , aa 20 , aa 21 , aa 22 is the linker amino acid U covalently attached to the surfactant X.

13 . (canceled)

14 . The peptide product of claim 1 , wherein the surfactant X has the structure:

wherein:

A is a substituted or unsubstituted C 1 -C 30 alkyl chain, a substituted or unsubstituted alkoxyaryl group, a substituted or unsubstituted aralkyl group;

R 1b , R 1c , and R 1d are each, independently at each occurrence, H, a protecting group, or a substituted or unsubstituted C 1 -C 30 alkyl group;

W 1 is independently, at each occurrence, —CH 2 —, —CH 2 —O—, —(C═O), —(C═O)—O—, —(C═O)—NH—, —(C═S)—, —(C═S)—NH—, or —CH 2 —S—;

W 2 is —O— or —S—;

R 2 is a bond to U.

15 . The peptide product of claim 14 , wherein the surfactant X has the structure:

16 . The peptide product of claim 14 , wherein the surfactant X has the structure:

17 . The peptide product of claim 14 , wherein the surfactant X has the structure:

wherein:

A is a substituted C 3 -C 20 alkyl group;

R 1b , R 1c , and R 1d are each, independently at each occurrence, H, a protecting group, or a substituted or unsubstituted C 1 -C 30 alkyl group;

W 1 is —(C═O)—NH—;

W 2 is —O—;

R 2 is a bond to U.

18 . The peptide product of claim 14 , wherein the surfactant X has the structure:

wherein:

A is a substituted C 3 -C 20 alkyl group;

R 1b , R 1c , and R 1d are H;

W 1 is —(C═O)—NH—;

W 2 is —O—; and

R 2 is a bond to U.

19 . The peptide product of claim 1 , wherein the hydrophobic group A is a substituted or unsubstituted C 6 -C 18 alkyl group and the hydrophilic group is selected from glucose, maltose, glucuronic acid, diglucuronic acid or maltouronic acid.

20 - 37 . (canceled)

38 . A pharmaceutical composition comprising a therapeutically effective amount of the peptide product of claim 1 , or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.

39 . A method for improving the pharmaceutical and medicinal behavior of a peptide, thereby improving its duration of action, bioavailability or its stability in formulation, comprising covalent attachment of a surfactant X to the peptide, wherein X is as defined in claim 1 .

40 . (canceled)