Peptides that block the binding of IgG to FcRn
The invention relates to peptides which bind to human FcRn and inhibit binding of the Fc portion of an IgG to an FcRn, thereby modulating serum IgG levels. The disclosed compositions and methods may be used for example, in treating autoimmune diseases and inflammatory disorders. The invention also relates to methods of using and methods of making the peptides of the invention.
1. A monomeric peptide comprising:
-Gly-H 6 -F 7 -G 8 -G 9 -X 10 -Y 11 - (SEQ ID NO: 324)
wherein:
H 6 is histidine or is selected from a positively charged amino acid, a positively charged amino acid analog, an aromatic amino acid, an aromatic amino acid analog, a positively charged aromatic amino acid, and a positively charged aromatic amino acid analog;
F 7 is phenylalanine or a phenylalanine analog,
G 8 and G 9 are each glycine, or are independently selected from a glycine analog, sarcosine, a sarcosine analog, aspartic acid, an aspartic acid analog, a D -amino acid, a D -amino acid analog, α-aminoisobutyric acid, and an α-aminoisobutyric acid analog, or
G 8 when together with G 9 , forms a dipeptide mimetic;
X 10 is an amino acid or an amino acid analog, or
X 10 , when taken together G 9 , forms a dipeptide mimetic;
Y 11 is tyrosine; and
wherein the peptide is 10 to 50 amino acids and/or amino acid analogs in length and is capable of binding to human Fc neonatal receptor (FcRn).
2. The peptide of claim 1 , comprising:
R 1 -Gly-H 6 -F 7 -G 8 -G 9 -X 10 -Y 11 -R 2 (SEQ ID NO: 325)
wherein:
R 1 has the formula X 1 -X 2 -X 3 -X 4 -
wherein:
X 1 is chosen from hydrogen, acyl, and an amino protecting group;
X 2 is absent or is 1-15 amino acids and/or amino acid analogs in length;
X 3 is absent or is an amino acid or amino acid analog that is capable of forming a bridge with X 10 , X 12 or X 13 , wherein the bridge is chosen from an amino terminus to carboxy terminus bridge, a side chain to backbone bridge, and a side chain to side chain bridge;
X 4 is absent or is 1-15 amino acids and/or amino acid analogs in length;
R 2 has the formula -X 12 -X 13 -X 14 -X 15
wherein:
X 12 is absent or is an amino acid or amino acid analog;
X 13 is absent or is an amino acid or amino acid analog;
X 14 is 1-15 amino acids and/or amino acid analogs in length; and
X 15 is an amino group or a carboxy protecting group.
3. The peptide of claim 1 , wherein the peptide is 11-35 amino acids and/or amino acid analogs in length (SEQ ID NO: 326).
4. The peptide of claim 1 , wherein the peptide is 10-30 amino acids and/or amino acid analogs in length (SEQ ID NO: 327).
5. A peptide, comprising the sequence:
wherein:
R 6 is chosen from
R 7 is chosen from
G 8 and G 9
are each independently chosen from
wherein R is chosen from
when taken together, form a dipeptide mimetic chosen from:
X 10
is chosen from
when taken together with G 9 , forms a dipeptide mimetic chosen from
R 11 is chosen from
wherein the peptide is 10 to 50 amino acids and/or amino acid analogs in length and is capable of binding to human Fc neonatal receptor (FcRn).
6. The peptide of claim 5 , comprising:
wherein R 6 is chosen from:
wherein R 7 is chosen from:
wherein G 8 is chosen from:
wherein G 8 and G 9
are each independently chosen from:
wherein R is chosen from:
when taken together, form a dipeptide chosen from:
when taken together, form a dipeptide mimetic chosen from:
wherein X 10 is chosen from:
wherein G 9 , taken together with X 10 , forms a dipeptide mimetic chosen from:
wherein R 11 is chosen from:
7. The peptide of claim 2 , wherein X 2 is 1-3 amino acids and/or amino acid analogs in length.
8. The peptide of claim 2 , wherein X 3 is an amino acid or amino acid analog that is capable of forming a bridge with X 10 , X 12 , or X 13 .
9. The peptide of claim 1 , wherein H 6 is a positively charged aromatic amino acid or a positively charged aromatic amino acid analog.
10. The peptide of claim 1 , wherein H 6 is histidine.
11. The peptide of claim 5 , wherein R 6 is
12. The peptide of claim 1 , wherein F 7 is phenylalanine.
13. The peptide of claim 5 , wherein R 7 is
14. The peptide of claim 1 , wherein at least one of G 8 and G 9 is a D -amino acid, α-aminoisobutyric acid, or sarcosine.
15. The peptide of claim 1 , wherein X 10 is a neutral amino acid, neutral amino acid analog, hydrophobic amino acid, or hydrophobic amino acid analog.
16. The peptide of claim 5 , wherein R 11 is
17. The peptide of claim 5 , wherein R 6 is
R 7 is
and R 11 is
18. The peptide of claim 1 or claim 5 , wherein the peptide is linear.
19. The peptide of claim 2 , wherein at least one of X 10 , X 12 , and X 13 is an amino acid or amino acid analog that is capable of forming a bridge with X 3 , wherein the bridge is chosen from an amino terminus to carboxy terminus bridge, a side chain to backbone bridge, and a side chain to side chain bridge.
20. The peptide of claim 19 , wherein X 3 forms a bridge with X 10 , X 12 , or X 13 .
21. The peptide of claim 20 , wherein the peptide has nine amino acids and/or amino acid analogs between the amino acids and/or amino acid analogs forming the bridge.
22. The peptide of claim 19 , wherein the side chain to side chain bridge is a disulfide bridge, an ether bridge, a thioether bridge, an alkene bridge, or an amide bridge.
23. The peptide of claim 22 , wherein the side chain to side chain bridge is either
(a) a disulfide bridge between:
cysteine and cysteine;
cysteine and homocysteine;
cysteine and penicillamine;
homocysteine and homocysteine;
homocysteine and penicillamine; and
penicillamine and penicillamine, or
(b) an amide bridge between:
aspartic acid and lysine;
aspartic acid and ornithine;
aspartic acid and 2,4-diaminobutyric acid;
aspartic acid and 2,3-diaminopropionic acid;
glutamic acid and lysine;
glutamic acid and ornithine;
glutamic acid and 2,4-diaminobutyric acid; and
glutamic acid and 2,3-diaminopropionic acid.
24. The peptide of claim 1 , comprising:
Gly-H 6 -Phe-G 8 -G 9 -X 10 -Tyr (SEQ ID NO: 326).
25. The peptide of claim 1 , comprising:
Gly-His-Phe-Gly-Gly-X 10 -Tyr (SEQ ID NO: 327).
26. The peptide of claim 1 , comprising:
Gly-His-Phe-Gly-Sar-X 10 -Tyr (SEQ ID NO: 328).
27. The peptide of claim 2 , comprising:
Pen-Thr-Gly-His-Phe-Gly-Sar-X 10 -Tyr (SEQ ID NO: 329).
28. The peptide of claim 1 , comprising:
Arg-Phe-Pen-Thr-Gly-His-Phe-Gly-Sar-NMeLeu-Tyr-Pro-Cys (SEQ ID NO: 330).
29. A peptide comprising the sequence:
SEQ ID
NO:
1
QRFCTGHFGGLYPCNGP;
2
GGGCVTGHFGGIYCNYQ;
3
KIICSPGHFGGMYCQGK;
4
PSYCIEGHIDGIYCFNA;
5
NSFCRGRPGHFGGCYLF;
6
AGQRFCTGHFGGLYPCNGPGTGGGK;
7
AGGGCVTGHFGGIYCNTQGTGGGK;
8
AGKIICSPGHFGGMYCQGKGTGGGK;
9
AGPSYCIEGHIDGIYCFNAGTGGGK;
10
AGNSFCRGRPGHFGGCYLFGTGGGK;
17
CTGHFGGLYPCNGP;
18
QRFCTGHFGGLYPC;
19
CTGHFGGLYPC;
20
TGHFGGLYP;
21
RFCTGHFGGLYPCNGP;
22
FCTGHFGGLYPCNGP;
23
QRFCTGHFGGLYPCNG;
24
QRFCTGHFGGLYPCN;
25
QAFCTGHFGGLYPCNGP;
26
QRACTGHFGGLYPCNGP;
27
QRFCAGHFGGLYPCNGP;
28
QRFCTAHFGGLYPCNGP;
29
QRFCTGAFGGLYPCNGP;
30
QRFCTGHAGGLYPCNGP;
31
QRFCTGHFAGLYPCNGP;
32
QRFCTGHFGALYPCNGP;
33
QRFCTGHFGGAYPCNGP;
34
QRFCTGHFGGLAPCNGP;
35
QRFCTGHFGGLYACNGP;
36
QRFCTGHFGGLYPCAGP;
197
QRFCTGHFaGLYPCNGP;
198
QRFCTGHFGaLYPCNGP;
199
QRFCTGHFaaLYPCNGP;
200
QRFCGHF-betaAla-LYPCNGP;
146
QRFCTGHFGGLFPCNGP;
37
QRFCTGHFGGLYP-hC-NGP;
38
QRF-hC-TGHFGGLYP-hC-NGP;
39
QRFcTGHFGGLYPCNGP;
40
QRFCTGHFGGLYPcNGP;
41
QRFcTGHFGGLYPcNGP;
42
QRF-Pen-TGHFGGLYPCNGP;
43
QRFCTGHFGGLYP-Pen-NGP;
44
QRF-Pen-TGHFGGLYP-Pen-NGP;
201
QRFCTGHF-Apa-LYPCNGP;
168
QRFCTG-Dab-FGGLYPCNGP;
220
QRFDTGHFGGLYP-Dab-NGP;
221
QRFDTGHFGGLYPKNGP;
71
QRF-Pen-TGHFGpLYPCNGP;
72
QRF-Pen-TGHFGrLYPCNGP;
73
QRF-Pen-TGHFGhLYPCNGP;
74
QRF-Pen-TGHFGiLYPCNGP;
75
QRF-Pen-TGHFGfLYPCNGP;
76
QRF-Pen-TGHFGyLYPCNGP;
77
QRF-Pen-TGHFG-Aib-LYPCNGP;
78
QRF-Pen-TGHFdGLYPCNGP;
79
QRF-Pen-TGHFpGLYPCNGP;
80
QRF-Pen-TGHFrGLYPCNGP;
81
QRF-Pen-TGHFhGLYPCNGP;
82
QRF-Pen-TGHFiGLYPCNGP;
83
QRF-Pen-TGHFfGLYPCNGP;
84
QRF-Pen-TGHFyGLYPCNGP;
85
QRF-Pen-TGHF-Aib-GLYPCNGP;
121
QRF-Pen-TGH-(4-amino-Phe)-GGLYPCNGP;
122
QRF-Pen-TGH-(4-methoxy-Phe)-GGLYPCNGP;
123
QRF-Pen-TGH-(pentafluoro-Phe)-GGLYPCNGP;
124
QRF-Pen-TGH-(2-pyridylalanine)-GGLYPCNGP;
250
QRFVTGHFpGLYPANGP;
125
QRF-Pen-TGH-(3-PyridylAla)-GGLYPCNGP;
126
QRF-Pen-TGH-(4-nitro-Phe)-GGLYPCNGP;
127
QRF-Pen-TGH-(1-napthylalanine)-GGLYPCNGP;
128
QRF-Pen-TGH-(2-napthylalanine)-GGLYPCNGP;
148
QRF-Pen-TGHFGGL-(4-amino-Phe)-PCNGP;
149
QRF-Pen-TGHFGGL-(4-methoxyPhe)-PCNGP;
150
QRF-Pen-TGHFGGL-(pentafluoroPhe)-PCNGP;
151
QRF-Pen-TGHFGGL-(2-pyridylAla)-PCNGP;
152
QRF-Pen-TGHFGGL-(3-pyridylAla)-PCNGP;
153
QRF-Pen-TGHFGGL-(4-nitro-Phe)-PCNGP;
45
QRF-Pen-TGHFGGLYP-hC-NGP;
46
QRF-hC-TGHFGGLYP-Pen-NGP;
247
QRFSTGHFGGLYPSNGP;
222
QRF-Dab-TGHFGGLYPENGP;
223
QRFKTGHFGGLYPENGP;
86
QRF-Pen-TGHFGaLYPCNGP;
87
QRF-Pen-TGHFaGLYPCNGP;
224
QRFETGHFGGLYPKNGP;
225
QRFETGHFGGLYP-Dab-NGP;
226
QRFETGHFGGLYP-Dap-NGP;
227
QRFDTGHFGGLYP-Dap-NGP;
210
RF-Pen-TGHF-X-LYPC, wherein X = 3-amino-N-1-carboxy-
methyl-2,3,4,5-tetrahydro-1H-[1]-benzazepine-2-one =
228
QRFKTGHFGGLYPDNGP;
229
QRF-Dab-TGHFGGLYPDNGP;
62
F-Pen-TGHFGGLYPC;
157
QRF-Pen-TGHFGGHYPCNGP;
230
QRFDTGHFGGLYP-Orn-NGP;
231
QRFETGHFGGLYP-Orn-NGP;
154
QRF-Pen-TGHFGGL-(2-nitro-Tyr)-PCNGP;
129
QRF-Pen-TGH-(2-MePhe)-GGLYPCNGP;
130
QRF-Pen-TGH-(3-MePhe)-GGLYPCNGP;
131
QRF-Pen-TGH-(4-MePhe)-GGLYPCNGP;
170
QRF-Pen-TG-Thz-FGGLYPCNGP;
132
QRF-Pen-TGH-(homoPhe)-GGLYPCNGP;
133
QRF-Pen-TGH-(Cha)-GGLYPCNGP;
134
QRF-Pen-TGH-(PheNHAc)-GGLYPCNGP;
135
QRF-Pen-TGHWGGLYPCNGP;
100
QRf-Pen-TGHFGGLYPCNGP;
101
QRY-Pen-TGHFGGLYPCNGP;
102
QRW-Pen-TGHFGGLYPCNGP;
64
RF-Pen-TGHFGGLYPC;
158
QRF-Pen-TGHFGGIYPCNGP;
136
QRF-Pen-TGH-(phenylGly)-GGLYPCNGP;
137
QRF-Pen-TGH-(Tic)-GGLYPCNGP;
138
QRFDTGH-(2MePhe)-GGLYPKNGP;
233
QRFDTGHFGaLYPKNGP;
234
QRFDTGHFaGLYPKNGP;
239
QRFDTGHFGGLYKNGP;
50
QRF-Pen-T-Sar-HFGGLYPCNGP;
171
QRF-Pen-TG-Dap-FGGLYPCNGP;
52
QRF-Pen-TGH-NMePhe-GGLYPCNGP;
53
QRF-Pen-TGHF-Sar-GLYPCNGP;
54
QRF-Pen-TGHFG-Sar-LYPCNGP;
55
QRF-Pen-TGHFGG-NMeLeu-YPCNGP;
56
QRF-Pen-TGHFGGL-NMeTyr-PCNGP;
159
QRF-Pen-TGHFGGFYPCNGP;
160
QRF-Pen-TGHFGGWYPCNGP;
161
QRF-Pen-TGHFGGMYPCNGP;
162
QRF-Pen-TGHFGGLYPCNGP;
235
DTGHFGGLYPKNGP;
236
FDTGHFGGLYPKNGP;
237
RFDTGHFGGLYPKNGP;
238
QRFDTGHFGGLYPKNGP;
239
QRFDTGHFGGLYPKN;
240
QRF-Dap-TGHFGGLYPDNGP;
241
QRF-Dap-TGHFGGLYPENGP;
242
QRF-Orn-TGHFGGLYPDNGP;
243
QRF-Orn-TGHFGGLYPENGP;
244
RFDTGHFGGLYPK;
245
QRFDTGHFGGLYPK;
203
RF-Pen-TGHF-X-LYPC, wherein X =
4-aminomethyl-benzoic acid =
204
RF-Pen-TGHF-X-LYPC, wherein
X = (3-aminomethyl)-benzoic acid =
205
RF-Pen-TGHF-X-LYPC, wherein X =
4-aminophenyl acetic acid =
206
RF-Pen-TGHF-X-LYPC, wherein X =
3-aminophenyl acetic acid =
173
QRF-Pen-TG-(1Me)His-FGGLYPCNGP;
174
QRF-Pen-TG-Dab-FGGLYPCNGP;
155
QRF-Pen-TGHFGGL-(4-fluoro-Phe)-PCNGP;
65
QRF-Pen-TGHFGpLYPC;
66
RF-Pen-TGHFGpLYPC;
67
F-Pen-TGHFGpLYPC;
68
RF-Pen-TGHFGpLYPCNGP;
69
F-Pen-TGHFGpLYPCNGP;
57
RF-Pen-TGHFGG-NMeLeu-YPCNGP;
58
RF-Pen-TGHFG-Sar-YPCNGP;
88
QRF-Pen-TGHFaaLYPCNGP;
89
QRF-Pen-TGHFapLYPCNGP;
90
QRF-Pen-TGHFfpLYPCNGP;
91
QRF-Pen-TGHFfaLYPCNGP;
92
QRF-Pen-TGHFppLYPCNGP;
93
QRF-Pen-TGHFfG-NMeLeu-YPCNGP;
94
QRF-Pen-TGHFaG-NMeLeu-YPCNGP;
95
QRF-Pen-TGHFfGPYPCNGP;
248
QRFVTGHFppLYPANGP;
249
QRFVTGHFGpLYPANGP;
246
QRFDTGHFGpLYPKNGP;
251
QRFLTGHFGpLYPANGP;
252
QRFITGHFGpLYPANGP;
253
QRFFTGHFGpLYPANGP;
254
QRFYTGHFGpLYPANGP;
255
QRFWTGHFGpLYPANGP;
256
QRFVTGHFGpLYPVNGP;
257
QRFVTGHFGpLYPLNGP;
258
QRFVTGHFGpLYPINGP;
259
QRFVTGHFGpLYPFNGP;
260
QRFVTGHFGpLYPYNGP;
261
QRFVTGHFGpLYPWNGP;
262
QRFVTGHFGpVYPANGP;
263
QRFVTGHFGpIYPANGP;
264
QRFVTGHFGpFYPANGP;
265
QRFVTGHFGpYYPANGP;
266
QRFVTGHFGpWYPANGP;
207
RF-Pen-TGHF-X-LYPC, wherein X = 3-amino-2-oxo-1-
piperidine-acetic acid =
208
RF-Pen-TGHF-X-LYPC, wherein X = 3-amino-2-oxo-1-
piperidine-acetic acid =
210
RF-Pen-TGHF-X-LYPC, wherein X = 3-amino-N-1-carboxy-
methyl-2,3,4,5-tetrahydro-1H-[1]-benzazepine-2-one =
275
RFVTGHF-X-LYPA, wherein X = 3-amino-2-oxo-1-
piperidine-acetic acid =
276
RFVTGHF-X-LYPA, wherein X = 3-amino-2-oxo-1-
piperidine-acetic acid =
277
RFVTGHF-X-LYPA, wherein X = 3-amino-N-1-carboxy-
methyl-2,3,4,5-tetrahydro-1H-[1]-benzazepine-2-one =
278
RFVTGHF-X-LYPA, wherein X = 3-amino-N-1-carboxy-
methyl-2,3,4,5-tetrahydro-1H-[1]-benzazepine-2-one =
279
RFVTGHF-X-LYPA, wherein X = 3-aminophenyl acetic acid =
59
QRF-Pen-TGHFG-Sar-NMeLeu-YPCNGP;
108
QRF-Pen-TGHFa-Sar-NMeLeu-YPCNGP;
98
QRF-Pen-TGHFa-Sar-LYPCNGP;
267
QRFVTGHFGpWYPINGP;
280
QRFVTGHF-X-WYPINGP, wherein X = 3-amino-2-oxo-1-
piperidine-acetic acid =
51
RF-Pen-TG-NMeHis-FGGLYPC;
209
RF-Pen-TGHF-X-LYPC, wherein X = 3(S)-3-amino-2-oxo-1-
piperidine-acetic acid =
167
QRF-Pen-TGHFG-X-YPCNGP, wherein
X = D,L-Friedinger's lactam =
105
QRF-Pen-GGHFGGLYPCNGP;
48
QRFC-NMeAla-GHFGGLYPCNGP;
212
RF-Pen-TGHF-X-LYPC, wherein X = 5,5-bicyclic
dipeptide mimic =
213
RF-Pen-TGHF-X-LYPC, wherein X = 5,5-bicyclic
dipeptide mimic =
96
QRF-Pen-TGHFpPLYPCNGP;
97
QRF-Pen-TGHFfPLYPCNGP;
214
RF-Pen-TGHF-X-LYPC, wherein X = 6,5-bicyclic
dipeptide mimic =
215
RF-Pen-TGHF-X-LYPC, wherein X = (R)-2-(3-amino-2-
oxoazepan-1-yl)acetic acid =
281
RFVTGHF-X-LYPA, wherein X = 5,5-bicyclic
dipeptide mimic =
282
RFVTGHF-X-LYPA, wherein X = 6,5-bicyclic
dipeptide mimic =
283
RFVTGHF-X-LYPA, wherein X = (R)-2-(3-amino-2-
oxoazepan-1-yl)acetic acid =
268
RFVTGHFGpWYP;
269
RFVTGHFGpWYPANGP;
270
FVTGHFGpWYPA;
271
VTGHFGpWYPA;
106
QRF-Pen-(NMeAla)-GHFGGLYPCNGP;
216
RF-Pen-TGHF-X-LYPC, wherein X = (R)-2-(3-amino-2-
oxopyrrolidin-1-yl)acetic acid =
166
QRF-Pen-TGHFG-X-YPCNGP,
wherein X = L,L-Friedinger's lactam =
110
RF-Pen-TGHFf-Sar-NMeLeu-YPC;
111
RF-Pen-TGHFv-Sar-NMeLeu-YPC;
112
RF-Pen-TGHFl-Sar-NMeLeu-YPC;
113
RF-Pen-TGHFw-Sar-NMeLeu-YPC;
139
RF-Pen-TGH-(2-Cl-Phe)-GGLYPC;
140
RF-Pen-TGH-(3-Cl-Phe)-GGLYPC;
141
RF-Pen-TGH-(4-Cl-Phe)-GGLYPC;
142
RF-Pen-TGH-(3,3-Di-Phe)-GGLYPC;
143
RF-Pen-TGH-(4,4-Bi-Phe)-GGLYPC;
144
RF-Pen-TGH-(4-t-Butyl-Phe)-GGLYPC;
286
RF-Pen-TGHF-X-NMeLeu-YPC, wherein X = 3(R)-3-
amino-2-oxo-1-piperidine-acetic acid =
287
RF-Pen-NMeAla-GHF-X-NMeLeu-YPC, wherein X =
3(R)-3-amino-2-oxo-1-piperidine-acetic acid =
60
RF-Pen-TGHFG-Sar-NMeLeu-YPC;
272
RFVTGHFG-Sar-NMeLeu-YPA;
163
RF-Pen-TGHFGGWYPC;
164
QRF-Pen-TGHFG-Sar-WYPCNGP;
219
RF-Pen-TGHF-X-NMeLeu-YPC, wherein X = (R)-2-(3-
amino-2-oxoazepan-1-yl)acetic acid =
114
RF-Pen-TGHFt-Sar-NMeLeu-YPC;
115
RF-Pen-TGHFs-Sar-NMeLeu-YPC;
116
RF-Pen-TGHFd-Sar-NMeLeu-YPC;
117
RF-Pen-TGHFn-Sar-NMeLeu-YPC;
118
RF-Pen-TGHFe-Sar-NMeLeu-YPC;
119
RF-Pen-TGHFq-Sar-NMeLeu-YPC;
273
RFVTGHFGpWYPA;
176
RF-Pen-TG-Thz-FG-Sar-NMeL-YPC;
177
RF-Pen-TG-2PyridylAla-FG-Sar-NMeL-YPC;
178
RF-Pen-TG-3PyridylAla-FG-Sar-NMeL-YPC;
179
RF-Pen-TG-ThienylAla-FG-Sar-NMeL-YPC;
180
RF-Pen-TG-Dab-FG-Sar-NMeL-YPC;
181
RF-Pen-TG-Orn-FG-Sar-NMeL-YPC;
182
RF-Pen-TGKFG-Sar-NMeL-YPC;
183
RF-Pen-TGRFG-Sar-NMeL-YPC;
184
RF-Pen-TG-4GuanylPhe-FG-Sar-NMeL-YPC;
185
RF-Pen-TG-4aminoPhe-FG-Sar-NMeL-YPC;
186
RF-Pen-TG-His(Me)-FGGLYPC;
187
RF-Pen-TG-His(Me)2-FGGLYPC;
188
RF-Pen-TG-PropargylGly-FG-Sar-NMeLeu-YPC;
189
RF-Pen-TG-(2-PyrrolidinylAla)-FG-Sar-NMeLeu-YPC;
190
RF-Pen-TG-(3-PiperidyalAla)-FG-Sar-NMeLeu-YPC;
191
RF-Pen-TG-(4-PiperidylAla)-FG-Sar-NMeLeu-YPC;
192
RF-Pen-TGFFG-Sar-NMeLeu-YPC;
193
RF-Pen-TGAFG-Sar-NMeLeu-YPC;
145
RF-Pen-TGH-((D/L)-betamethylPhe)-G-Sar-NMeLeu-YPC;
194
RF-Pen-TG-(4-PyridylAla)-FG-Sar-NMeLeu-YPC;
195
RF-Pen-TG-Thz(Me)-FG-Sar-NMeL-YPC;
196
RF-Pen-TG-triazolylAla-FG-Sar-NMeL-YPC;
47
QRF-Pen-TGHFGpLYP-Pen-NGP;
104
QRF-Pen-HGHFGGLYPCNGP; or
172
QRF-Pen-TG-Dap(Guanyl)-FGGLYPCNGP;
wherein the peptide is 10 to 50 amino acids and/or amino acid analogs in length and is capable of binding to human Fc neonatal receptor (FcRn).
30. A multimeric peptide comprising one or more monomeric peptides independently selected from peptides according to any one of claim 1 , 5 , or 29 .
31. A peptide comprising the structure:
32. The peptide of claim 30 , wherein the peptide is a dimer, a trimer, or a tetramer.
33. The peptide of claim 32 , wherein the peptide is a dimer.
34. The peptide of claim 33 , wherein the dimer is the product of a reaction between individual peptide monomers and a multivalent linker.
35. The peptide of claim 1 , wherein the peptide binds specifically to human FcRn and inhibits binding of human FcRn to human IgG.
36. A pharmaceutical composition comprising a therapeutically effective amount of the peptide of claim 30 .
37. The composition of claim 36 , wherein the therapeutically effective amount of the peptide is capable of decreasing the serum concentration of human IgG as compared to the serum concentration of human IgG before treatment with the peptide.
38. A method of regulating a disease state characterized by excessive serum levels of IgG, comprising contacting a cell with a therapeutically effective amount of a peptide according to claim 30 to decrease the serum concentration of human IgG as compared to the serum concentration of human IgG before treatment with the peptide.
39. The method according to claim 38 , further comprising regulating the disease state by modulating the serum concentration of IgG.
40. The method according to claim 38 , wherein the disease state is an inflammatory disease or an autoimmune disease.
41. The method according to claim 40 , wherein the autoimmune disease is chosen from alopecia areata, ankylosing spondylitis, antiphospholipid syndrome, autoimmune Addison's disease, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune lymphoproliferative syndrome, autoimmune thrombocytopenic purpura, Behcet's disease, bullous pemphigoid, cardiomyopathy, celiac sprue-dermatitis herpetiformis, chronic fatigue immune dysfunction syndrome, chronic inflammatory demyelinating polyneuropathy, cicatricial pemphigoid, CREST syndrome, cold agglutinin disease, Crohn's disease, Degos' disease, dermatomyositis, dermatomyositis-juvenile, discoid lupus, essential mixed cryoglobulinemia, fibromyalgia-fibromyositis, Graves' disease, Guillain-Barré, Hashimoto's thyroiditis, idiopathic pulmonary fibrosis, idiopathic thrombocytopenia purpura, IgA nephropathy, insulin dependent diabetes, juvenile arthritis, lichen planus, lupus, Ménière's disease, mixed connective tissue disease, multiple sclerosis, myasthenia gravis, pemphigus, pernicious anemia, polyarteritis nodosa, polychondritis, polyglandular syndromes, polymyalgia rheumatica, polymyositis and dermatomyositis, primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, Raynaud's phenomenon, Reiter's syndrome, rheumatic fever, rheumatoid arthritis, sarcoidosis, scleroderma, Sjögren's syndrome, stiff-man syndrome, takayasu arteritis, temporal arteritis (giant cell arteritis), transplant rejection, ulcerative colitis, uveitis, vasculitis, vitiligo, and Wegener's granulomatosis.
42. The method according to claim 41 , wherein the autoimmune disease is chosen from bullous pemphigoid, idiopathic thrombocytopenia purpura, myasthenia gravis, pemphigus, and transplant rejection.
43. The method according to claim 42 , wherein the pemphigus is pemphigus vulgaris.
44. The method according to claim 40 , wherein the inflammatory disease is chosen from asthma, ulcerative colitis and inflammatory bowel syndrome allergy, mastocytosis, and arthritis.