Peptide Information
General Information of This Peptide
| Peptide ID |
PEP00015
|
|||||
|---|---|---|---|---|---|---|
| Peptide Name |
AAM-2
|
|||||
| Structure |
|
|||||
| Sequence |
CIGAVLHVLTTGLPALISWIHHHHQQ-NH2
|
|||||
| Peptide Type |
Linear
|
|||||
| Receptor Name |
Cell membrane
|
|||||
| PDC Transmembrane Types | Cell-penetrating peptides (CPPs) | |||||
| Formula |
C132H206N40O31S
|
|||||
| Isosmiles |
[H]NC(=O)CC[C@H](NC(=O)[C@H](CCC(=O)N[H])NC(=O)[C@H](Cc1cn([H])cn1)NC(=O)[C@H](Cc1cn([H])cn1)NC(=O)[C@H](Cc1cn([H])cn1)NC(=O)[C@H](Cc1cn([H])cn1)NC(=O)[C@@]([H])(NC(=O)[C@H](Cc1cn([H])c2ccccc12)NC(=O)[C@H](CO[H])NC(=O)[C@@]([H])(NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@]([H])(NC(=O)[C@@]([H])(NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](Cc1cn([H])cn1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@]([H])(NC(=O)[C@H](CS[H])N[H])[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O[H])[C@@H](C)O[H])[C@@H](C)CC)[C@@H](C)CC)C(N)=O
|
|||||
| InChI |
InChI=1S/C132H206N40O31S/c1-23-68(16)104(167-112(183)82(133)56-204)125(196)143-53-100(178)150-71(19)111(182)165-102(66(12)13)127(198)161-86(37-62(4)5)114(185)160-94(46-80-52-141-61-149-80)122(193)166-103(67(14)15)128(199)162-88(39-64(8)9)120(191)170-108(74(22)175)131(202)171-107(73(21)174)126(197)144-54-101(179)152-95(40-65(10)11)132(203)172-36-28-31-97(172)124(195)151-72(20)110(181)155-87(38-63(6)7)119(190)168-106(70(18)25-3)130(201)164-96(55-173)123(194)156-89(41-75-47-142-83-30-27-26-29-81(75)83)121(192)169-105(69(17)24-2)129(200)163-93(45-79-51-140-60-148-79)118(189)159-92(44-78-50-139-59-147-78)117(188)158-91(43-77-49-138-58-146-77)116(187)157-90(42-76-48-137-57-145-76)115(186)154-85(33-35-99(135)177)113(184)153-84(109(136)180)32-34-98(134)176/h26-27,29-30,47-52,57-74,82,84-97,102-108,142,173-175,204H,23-25,28,31-46,53-56,133H2,1-22H3,(H2,134,176)(H2,135,177)(H2,136,180)(H,137,145)(H,138,146)(H,139,147)(H,140,148)(H,141,149)(H,143,196)(H,144,197)(H,150,178)(H,151,195)(H,152,179)(H,153,184)(H,154,186)(H,155,181)(H,156,194)(H,157,187)(H,158,188)(H,159,189)(H,160,185)(H,161,198)(H,162,199)(H,163,200)(H,164,201)(H,165,182)(H,166,193)(H,167,183)(H,168,190)(H,169,192)(H,170,191)(H,171,202)/t68-,69-,70-,71-,72-,73+,74+,82-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,102-,103-,104-,105-,106-,107-,108-/m0/s1
|
|||||
| InChIKey |
NROZBPIZWZOPIJ-LOXLAICCSA-N
|
|||||
| Pharmaceutical Properties |
Molecule Weight
|
2881.416
|
Polar area
|
1093.88
|
||
|
Complexity
|
2879.549341
|
xlogp Value
|
-7.8698
|
|||
|
Heavy Count
|
204
|
Rot Bonds
|
93
|
|||
|
Hbond acc
|
38
|
Hbond Donor
|
38
|
|||
Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
CPT-AAM-2 [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 |
55%
|
|||
| 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
|
||||
| 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
|
||||
| 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 |
57%
|
|||
| 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
|
||||
| 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
|
||||
| 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 |
74%
|
|||
| 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
|
||||
| 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
|
||||
| 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 |
86%
|
|||
| 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
|
||||
| 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 |
94%
|
|||
| 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
|
||||
| In Vitro Model | Mouse melanoma | B16-F10 cell | CVCL_0159 | ||
References