Peptide Information
General Information of This Peptide
| Peptide ID |
PEP00047
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| Peptide Name |
AAM-1
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| Structure |
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| Sequence |
GIGAVLHVLTTGLPALISWIHHHHQC-NH2
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| Peptide Type |
Linear
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| Receptor Name |
Cell membrane
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| PDC Transmembrane Types | Cell-penetrating peptides (CPPs) | |||||
| Formula |
C129H201N39O30S
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| Isosmiles |
[H]NCC(=O)N[C@]([H])(C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cn([H])cn1)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@]([H])(C(=O)N[C@]([H])(C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@]([H])(C(=O)N[C@@H](CO[H])C(=O)N[C@@H](Cc1cn([H])c2ccccc12)C(=O)N[C@]([H])(C(=O)N[C@@H](Cc1cn([H])cn1)C(=O)N[C@@H](Cc1cn([H])cn1)C(=O)N[C@@H](Cc1cn([H])cn1)C(=O)N[C@@H](Cc1cn([H])cn1)C(=O)N[C@@H](CCC(=O)N[H])C(=O)N[C@@H](CS[H])C(N)=O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O[H])[C@@H](C)O[H])C(C)C)C(C)C)[C@@H](C)CC
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| InChI |
InChI=1S/C129H201N39O30S/c1-23-67(16)102(161-97(173)45-130)122(191)139-52-98(174)146-70(19)109(178)162-100(65(12)13)124(193)156-83(35-61(4)5)111(180)155-91(44-79-51-137-60-145-79)119(188)163-101(66(14)15)125(194)157-85(37-63(8)9)117(186)166-106(73(22)171)128(197)167-105(72(21)170)123(192)140-53-99(175)148-92(38-64(10)11)129(198)168-34-28-31-95(168)121(190)147-71(20)108(177)150-84(36-62(6)7)116(185)164-104(69(18)25-3)127(196)159-93(54-169)120(189)151-86(39-74-46-138-81-30-27-26-29-80(74)81)118(187)165-103(68(17)24-2)126(195)158-90(43-78-50-136-59-144-78)115(184)154-89(42-77-49-135-58-143-77)114(183)153-88(41-76-48-134-57-142-76)113(182)152-87(40-75-47-133-56-141-75)112(181)149-82(32-33-96(131)172)110(179)160-94(55-199)107(132)176/h26-27,29-30,46-51,56-73,82-95,100-106,138,169-171,199H,23-25,28,31-45,52-55,130H2,1-22H3,(H2,131,172)(H2,132,176)(H,133,141)(H,134,142)(H,135,143)(H,136,144)(H,137,145)(H,139,191)(H,140,192)(H,146,174)(H,147,190)(H,148,175)(H,149,181)(H,150,177)(H,151,189)(H,152,182)(H,153,183)(H,154,184)(H,155,180)(H,156,193)(H,157,194)(H,158,195)(H,159,196)(H,160,179)(H,161,173)(H,162,178)(H,163,188)(H,164,185)(H,165,187)(H,166,186)(H,167,197)/t67-,68-,69-,70-,71-,72+,73+,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,100-,101-,102-,103-,104-,105-,106-/m0/s1
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| InChIKey |
SSISKAXCUYBBAC-GZRKIABJSA-N
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| Pharmaceutical Properties |
Molecule Weight
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2810.337
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Polar area
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1050.79
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Complexity
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2808.512227
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xlogp Value
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-7.5039
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Heavy Count
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199
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Rot Bonds
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90
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Hbond acc
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37
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Hbond Donor
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37
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Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
CPT-AAM-1 [Investigative]
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Cell survival rate |
43%
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| Administration Time | 72 h | ||||
| Administration Dosage | 10 µM | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginines and lysines with histidines. Importantly, we found that the conjugation of cargoes to the N-terminus of melittin analogs decreased their cell-penetrating and membrane-lytic activity compared to the C-terminus, implying that the C-terminus of analogs is more suitable for cargo conjugation. After the attachment of CPT, CPT-AAM-1 and CPT-AAM-2 displayed obvious pH-responsive antitumor activity. CPT-AAM-1 and CPT-AAM-2 destroyed tumor cells through the release of CPT and membrane disruption. Compared with CPT-AAM-2, CPT-AAM-1 showed stronger antitumor activity under acidic conditions. Notably, CPT-AAM-1 significantly inhibited the tumor growth in vivo compared with AAM, AAM-1, and CPT. In addition, CPT-AAM-1 showed relatively low toxicity compared with melittin and CPT. Taken together, our results demonstrate that CPT-AAM-1, with efficient pH-responsive cell-penetrating and membrane-lytic activities, possesses significant therapeutic potential for tumor therapy. This study provides a novel strategy for the development of PDCs based on pH-responsive AMPs for oncology therapeutics.
Click to Show/Hide
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| Description |
Subsequently, the cytotoxicity of these conjugates against B16-F10 cells was determined. As shown in Fig. 4B, CPT-AAM-1 and CPT-AAM-2 displayed significant pH-dependent antitumor activity after 72 h of treatment, whereas the cytotoxicity of CPT showed no obvious difference at pH 7.4 and 5.5. Notably, CPT-AAM-1 and CPT-AAM-2 exhibited greater cytotoxicity than free CPT under acidic conditions, particularly at high concentrations. Compared to CPT-AAM-2, CPT-AAM-1 displayed strong antitumor activity, suggesting that AAM-1 could deliver more CPT molecules into cells. In addition, this result further demonstrates that the C-terminus of AAM is more suitable for drug conjugation than the N-terminus.
Click to Show/Hide
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| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Cell survival rate |
60%
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| Administration Time | 72 h | ||||
| Administration Dosage | 5 µM | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginines and lysines with histidines. Importantly, we found that the conjugation of cargoes to the N-terminus of melittin analogs decreased their cell-penetrating and membrane-lytic activity compared to the C-terminus, implying that the C-terminus of analogs is more suitable for cargo conjugation. After the attachment of CPT, CPT-AAM-1 and CPT-AAM-2 displayed obvious pH-responsive antitumor activity. CPT-AAM-1 and CPT-AAM-2 destroyed tumor cells through the release of CPT and membrane disruption. Compared with CPT-AAM-2, CPT-AAM-1 showed stronger antitumor activity under acidic conditions. Notably, CPT-AAM-1 significantly inhibited the tumor growth in vivo compared with AAM, AAM-1, and CPT. In addition, CPT-AAM-1 showed relatively low toxicity compared with melittin and CPT. Taken together, our results demonstrate that CPT-AAM-1, with efficient pH-responsive cell-penetrating and membrane-lytic activities, possesses significant therapeutic potential for tumor therapy. This study provides a novel strategy for the development of PDCs based on pH-responsive AMPs for oncology therapeutics.
Click to Show/Hide
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| Description |
Subsequently, the cytotoxicity of these conjugates against B16-F10 cells was determined. As shown in Fig. 4B, CPT-AAM-1 and CPT-AAM-2 displayed significant pH-dependent antitumor activity after 72 h of treatment, whereas the cytotoxicity of CPT showed no obvious difference at pH 7.4 and 5.5. Notably, CPT-AAM-1 and CPT-AAM-2 exhibited greater cytotoxicity than free CPT under acidic conditions, particularly at high concentrations. Compared to CPT-AAM-2, CPT-AAM-1 displayed strong antitumor activity, suggesting that AAM-1 could deliver more CPT molecules into cells. In addition, this result further demonstrates that the C-terminus of AAM is more suitable for drug conjugation than the N-terminus.
Click to Show/Hide
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| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Cell survival rate |
62%
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| Administration Time | 72 h | ||||
| Administration Dosage | 2.5 µM | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginines and lysines with histidines. Importantly, we found that the conjugation of cargoes to the N-terminus of melittin analogs decreased their cell-penetrating and membrane-lytic activity compared to the C-terminus, implying that the C-terminus of analogs is more suitable for cargo conjugation. After the attachment of CPT, CPT-AAM-1 and CPT-AAM-2 displayed obvious pH-responsive antitumor activity. CPT-AAM-1 and CPT-AAM-2 destroyed tumor cells through the release of CPT and membrane disruption. Compared with CPT-AAM-2, CPT-AAM-1 showed stronger antitumor activity under acidic conditions. Notably, CPT-AAM-1 significantly inhibited the tumor growth in vivo compared with AAM, AAM-1, and CPT. In addition, CPT-AAM-1 showed relatively low toxicity compared with melittin and CPT. Taken together, our results demonstrate that CPT-AAM-1, with efficient pH-responsive cell-penetrating and membrane-lytic activities, possesses significant therapeutic potential for tumor therapy. This study provides a novel strategy for the development of PDCs based on pH-responsive AMPs for oncology therapeutics.
Click to Show/Hide
|
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| Description |
Subsequently, the cytotoxicity of these conjugates against B16-F10 cells was determined. As shown in Fig. 4B, CPT-AAM-1 and CPT-AAM-2 displayed significant pH-dependent antitumor activity after 72 h of treatment, whereas the cytotoxicity of CPT showed no obvious difference at pH 7.4 and 5.5. Notably, CPT-AAM-1 and CPT-AAM-2 exhibited greater cytotoxicity than free CPT under acidic conditions, particularly at high concentrations. Compared to CPT-AAM-2, CPT-AAM-1 displayed strong antitumor activity, suggesting that AAM-1 could deliver more CPT molecules into cells. In addition, this result further demonstrates that the C-terminus of AAM is more suitable for drug conjugation than the N-terminus.
Click to Show/Hide
|
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| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
| Experiment 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Cell survival rate |
72%
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| Administration Time | 72 h | ||||
| Administration Dosage | 1.25 µM | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginines and lysines with histidines. Importantly, we found that the conjugation of cargoes to the N-terminus of melittin analogs decreased their cell-penetrating and membrane-lytic activity compared to the C-terminus, implying that the C-terminus of analogs is more suitable for cargo conjugation. After the attachment of CPT, CPT-AAM-1 and CPT-AAM-2 displayed obvious pH-responsive antitumor activity. CPT-AAM-1 and CPT-AAM-2 destroyed tumor cells through the release of CPT and membrane disruption. Compared with CPT-AAM-2, CPT-AAM-1 showed stronger antitumor activity under acidic conditions. Notably, CPT-AAM-1 significantly inhibited the tumor growth in vivo compared with AAM, AAM-1, and CPT. In addition, CPT-AAM-1 showed relatively low toxicity compared with melittin and CPT. Taken together, our results demonstrate that CPT-AAM-1, with efficient pH-responsive cell-penetrating and membrane-lytic activities, possesses significant therapeutic potential for tumor therapy. This study provides a novel strategy for the development of PDCs based on pH-responsive AMPs for oncology therapeutics.
Click to Show/Hide
|
||||
| Description |
Subsequently, the cytotoxicity of these conjugates against B16-F10 cells was determined. As shown in Fig. 4B, CPT-AAM-1 and CPT-AAM-2 displayed significant pH-dependent antitumor activity after 72 h of treatment, whereas the cytotoxicity of CPT showed no obvious difference at pH 7.4 and 5.5. Notably, CPT-AAM-1 and CPT-AAM-2 exhibited greater cytotoxicity than free CPT under acidic conditions, particularly at high concentrations. Compared to CPT-AAM-2, CPT-AAM-1 displayed strong antitumor activity, suggesting that AAM-1 could deliver more CPT molecules into cells. In addition, this result further demonstrates that the C-terminus of AAM is more suitable for drug conjugation than the N-terminus.
Click to Show/Hide
|
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| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Melanoma | ||||
| Efficacy Data | Cell survival rate |
88%
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| Administration Time | 72 h | ||||
| Administration Dosage | 0.625 µM | ||||
| Evaluation Method | MTT assay | ||||
| MOA of PDC |
In this study, we developed novel melittin analogs with pH-responsive cell-penetrating and membrane-lytic activities by replacing arginines and lysines with histidines. Importantly, we found that the conjugation of cargoes to the N-terminus of melittin analogs decreased their cell-penetrating and membrane-lytic activity compared to the C-terminus, implying that the C-terminus of analogs is more suitable for cargo conjugation. After the attachment of CPT, CPT-AAM-1 and CPT-AAM-2 displayed obvious pH-responsive antitumor activity. CPT-AAM-1 and CPT-AAM-2 destroyed tumor cells through the release of CPT and membrane disruption. Compared with CPT-AAM-2, CPT-AAM-1 showed stronger antitumor activity under acidic conditions. Notably, CPT-AAM-1 significantly inhibited the tumor growth in vivo compared with AAM, AAM-1, and CPT. In addition, CPT-AAM-1 showed relatively low toxicity compared with melittin and CPT. Taken together, our results demonstrate that CPT-AAM-1, with efficient pH-responsive cell-penetrating and membrane-lytic activities, possesses significant therapeutic potential for tumor therapy. This study provides a novel strategy for the development of PDCs based on pH-responsive AMPs for oncology therapeutics.
Click to Show/Hide
|
||||
| Description |
Subsequently, the cytotoxicity of these conjugates against B16-F10 cells was determined. As shown in Fig. 4B, CPT-AAM-1 and CPT-AAM-2 displayed significant pH-dependent antitumor activity after 72 h of treatment, whereas the cytotoxicity of CPT showed no obvious difference at pH 7.4 and 5.5. Notably, CPT-AAM-1 and CPT-AAM-2 exhibited greater cytotoxicity than free CPT under acidic conditions, particularly at high concentrations. Compared to CPT-AAM-2, CPT-AAM-1 displayed strong antitumor activity, suggesting that AAM-1 could deliver more CPT molecules into cells. In addition, this result further demonstrates that the C-terminus of AAM is more suitable for drug conjugation than the N-terminus.
Click to Show/Hide
|
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| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
References