PEPTIDE PHARMACEUTICALS

1 . A biologically active peptide product that binds to GLP-1 receptor (GLP1R) and/or glucagon receptor (GCGR) comprising a surfactant X covalently attached to a peptide, the peptide comprising a linker amino acid U and at least one other amino acid:

wherein X is 1-alkyl glycoside

wherein

A is a hydrophobic group which is a substituted or unsubstituted C 8 -C 30 alkyl group; and

B is a hydrophilic saccharide covalently attached to the peptide via a linker amino acid U.

2 . The peptide product of claim 1 , wherein the peptide product is synthesized by reaction of a functionalized surfactant with the peptide.

3 . The peptide product of claim 1 , wherein the 1-alkyl glycoside is an O-linked, S-linked, N-linked or C-linked alkyl glycoside.

4 . The peptide product of claim 1 , wherein B is glucuronic acid.

5 . (canceled)

6 . (canceled)

7 . (canceled)

8 . The peptide product of claim 1 , wherein the hydrophilic group in the surfactant X is attached to the peptide via an amide bond.

9 . The peptide product of claim 1 , wherein the surfactant X comprises 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, 1-eicosyl beta-D-melibiouronic acid, 1-octadecyl beta-D-melibiouronic acid, 1-hexadecyl beta-D-melibiouronic acid, 1-tetradecyl beta-D-melibiouronic acid, 1-dodecyl beta-D-melibiouronic acid, 1-decyl beta-D-melibiouronic acid, 1-octyl beta-D-melibiouronic 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, 1-octyl beta-D-maltoside, 1-eicosyl beta-D-melibiose, 1-octadecyl beta-D-melibiose, 1-hexadecyl beta-D-melibiose, 1-tetradecyl beta-D-melibiose, 1-dodecyl beta-D-melibiose, 1-decyl beta-D-melibiose, or 1-octyl beta-D-melibiose.

10 . (canceled)

11 . The peptide product of claim 1 , wherein the peptide product comprises a sequence selected from Formula 3-II:

Formula 3-II

(SEQ. ID. NO. 303)

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 -aa 30 -aa 31 -

aa 32 -aa 33 -aa 34 -aa 35 -aa 36 -aa 37 -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 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;

aa 13 is absent or Tyr, Gln, Cit, or U;

aa 14 is absent or Leu, Met, Nle, or U;

aa 15 is absent or Asp, Glu, or U;

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

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

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

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

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

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

aa 22 is absent or Phe, Trp, Nal2, Aib, Ac4c, Ac5c, or U

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

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

aa 25 is absent or Trp, Nal2, or U;

aa 26 is absent or Leu, or U;

aa 27 is absent or Met, Val, Nle, Lys, or U;

aa 28 is absent or Asn, Lys, or U;

aa 29 is absent or Thr, Gly, Aib, Ac4c, Ac5c, or U;

aa 30 is absent or Lys, Aib, Ac4c, Ac5c, or U;

aa 31 is absent or Arg, Aib, Ac4c, Ac5c, or U;

aa 32 is absent or Asn, Aib, Ac4c, Ac5c, or U;

aa 33 is absent or Arg, Aib, Ac4c, Ac5c, or U;

aa 34 is absent or Asn, Aib, Ac4c, Ac5c, or U;

aa 35 is absent or Asn, Aib, Ac4c, Ac5c, or U;

aa 36 is absent or Ile, Aib, Ac4c, Ac5C, or U;

aa 36 is absent or Ala, Aib, Ac4c, Ac5C, or U;

aa 37 absent or U;

U is a natural or unnatural amino acid comprising a functional group used for covalent attachment to the surfactant X;

wherein any two of aa 1 -aa 37 are optionally cyclized through their side chains to form a lactam linkage; and

provided that one, or at least one of aa 11 aa 37 is the linker amino acid U covalently attached to the surfactant X.

12 . A peptide product of claim 1 , wherein the peptide product comprises a sequence selected from Formula 3-III-A:

Formula 3-III-A

(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

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 or Met, Val, Nle, Lys, or U(X);

aa 28 is absent or Asn, Lys, or U(X);

aa 29 is absent or Thr, Gly, Aib, Ac4c, Ac5c, or U(X);

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 , aa 25 , aa 26 , aa 27 , aa 28 or aa 29 is the linker amino acid U covalently attached to the surfactant X.

13 . The peptide product of claim 1 , wherein the peptide product comprises a sequence selected from has a structure of Formula 3-III-B:

Formula 3-III-B

(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 , aa 23 or aa 24 is the natural or unnatural amino acid U covalently attached to the surfactant X.

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

wherein:

A is a substituted or unsubstituted C 1 -C 20 alkyl chain;

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, C 2 -C 4 -alkene, C 2 -C 4 -alkyne, or —(CH 2 ) m -maleimide; and

m is 1-10.

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

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

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

wherein:

A is a substituted or unsubstituted C 8 -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 1 , wherein X has the structure:

wherein:

A is a substituted or unsubstituted C 8 -C 30 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 A is a substituted or unsubstituted C 8 -C 20 alkyl group.

20 - 37 . (canceled)

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

39 . (canceled)

40 . A method of inducing weigh loss comprising administering to a subject in need thereof a therapeutically effective amount of the peptide product of claim 1 .

41 . A method of preparing the peptide product of claim 1 wherein the peptide that binds to GLP-1 receptor (GLP1R) and/or glucagon receptor (GCGR) is synthesized using solid phase synthesis followed by acid-based deprotection and cleavage from a resin and purification by high performance liquid chromatography, wherein the surfactant X of claim 1 is covalently attached to the peptide to form the peptide product.

42 - 47 . (canceled)

48 . A method of treating metabolic syndrome, comprising administering to a subject in need thereof a therapeutically effective amount of the peptide product of claim 1 .

49 . The method of claim 48 , wherein the therapeutically effective amount is from about 0.1 mg/kg/day to about 100.0 mg/kg/day, or from about 0.01 mg/kg/day to about 1 mg/kg/day or from about 0.1 mg/kg/day to about 50 mg/kg/day.