PTD-DBM

PTD-DBM
Identifiers
CAS Number
PubChem CID
Chemical and physical data
FormulaC124H225N61O28S2
Molar mass3082.68 g·mol−1
3D model (JSmol)
  • CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC2=CN=CN2)NC(=O)CNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)N
  • InChI=1S/C124H225N61O28S2/c1-4-65(2)93(113(211)182-85(62-214)111(209)179-72(27-8-11-41-125)105(203)181-83(54-67-24-6-5-7-25-67)109(207)178-81(38-23-53-160-124(148)149)104(202)171-73(28-9-12-42-126)106(204)183-86(63-215)114(212)213)184-108(206)82(39-40-87(129)187)180-110(208)84(55-68-56-150-64-166-68)168-92(192)61-165-112(210)94(66(3)186)185-107(205)74(29-10-13-43-127)172-97(195)71(31-16-46-153-117(134)135)167-91(191)60-163-89(189)58-161-88(188)57-162-90(190)59-164-96(194)70(30-15-45-152-116(132)133)170-99(197)76(33-18-48-155-119(138)139)174-101(199)78(35-20-50-157-121(142)143)176-103(201)80(37-22-52-159-123(146)147)177-102(200)79(36-21-51-158-122(144)145)175-100(198)77(34-19-49-156-120(140)141)173-98(196)75(32-17-47-154-118(136)137)169-95(193)69(128)26-14-44-151-115(130)131/h5-7,24-25,56,64-66,69-86,93-94,186,214-215H,4,8-23,26-55,57-63,125-128H2,1-3H3,(H2,129,187)(H,150,166)(H,161,188)(H,162,190)(H,163,189)(H,164,194)(H,165,210)(H,167,191)(H,168,192)(H,169,193)(H,170,197)(H,171,202)(H,172,195)(H,173,196)(H,174,199)(H,175,198)(H,176,201)(H,177,200)(H,178,207)(H,179,209)(H,180,208)(H,181,203)(H,182,211)(H,183,204)(H,184,206)(H,185,205)(H,212,213)(H4,130,131,151)(H4,132,133,152)(H4,134,135,153)(H4,136,137,154)(H4,138,139,155)(H4,140,141,156)(H4,142,143,157)(H4,144,145,158)(H4,146,147,159)(H4,148,149,160)/t65-,66+,69-,70-,71-,72-,73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,93-,94-/m0/s1
  • Key:IMXABKONEGYGRF-QAMUXZJLSA-N

Protein transduction domain-fused dishevelled binding motif (PTD-DBM) is a synthetic peptide which interacts with the mechanism of the hair loss-linked endogenous protein, CXXC5, which is a negative feedback regulator of the Wnt/β-catenin pathway. Application of the peptide to bald laboratory mice resulted in new hair follicle growth.[1]

PTD-DBM is a peptide activating the Wnt/β-catenin signaling pathway functioning via interference of the binding of CXXC5 to dishevelled (Dvl), an upstream component of the Wnt/β-catenin pathway. By topical application, the PTD-DBM promotes the formation of new hair follicles and prevents hair loss. Combinatory treatment of PTD-DBM with valproic acid (VPA), the activator of Wnt/β-catenin pathway, further induce hair re-growth as well as wound-induced hair neogenesis (WIHN).[2][1] The increased expression of CXXC5 in the bald scalps and excellent effects of PTD-DBM on hair growth in mice raised hopes for the application of this peptide on hair growth in the clinic.

Discovery of PTD-DBM

Professor Kang-Yell Choi and his research team at Yonsei University in South Korea discovered a protein responsible for hair loss in the condition known as androgenetic alopecia. The responsible protein is called CXXC-type zinc finger protein 5 (CXXC5),[2] which acts as a negative regulator for the Wnt/β-catenin pathway, involved in hair regeneration and wound healing.[2][1] CXXC5 negatively regulates hair growth, and the researchers developed a new substance that promotes hair regeneration by controlling the function of CXXC5. When CXXC5 binds with the Dvl protein, which functions at the upstream of Wnt/β-catenin pathway, it suppresses hair regrowth and hair follicle neogenesis.[1] The observation of CXXC5 overexpression in the bald scalp by Professor Choi’s team led to the development of PTD-DBM, which interferes with the CXXC5-Dvl protein-protein interaction (PPI).[3][1] By topical application, PTD-DBM enhances hair regrowth as well as neogenesis.[1] The hair growth promoting effect of PTD-DBM is further enhanced when used in combination with a Wnt/β-catenin signaling activator such as VPA, which is generally used as a drug for bipolar disorder and activates the Wnt/β-catenin pathway by inhibition of GSK3β.[1] Currently, topical application of PTD-DBM or its combination with VPA has been used for treatment of hair loss.

References

  1. 1 2 3 4 5 6 7 Lee, Soung-Hoon; Seo, Seol Hwa; Lee, Dong-Hwan; Pi, Long-Quan; Lee, Won-Soo; Choi, Kang-Yell (November 2017). "Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis". Journal of Investigative Dermatology. 137 (11): 2260–2269. doi:10.1016/j.jid.2017.04.038. PMID 28595998.
  2. 1 2 3 Lee, Soung-Hoon; Kim, Mi-Yeon; Kim, Hyun-Yi; Lee, Young-Mi; Kim, Heesu; Nam, Kyoung Ae; Roh, Mi Ryung; Min, Do Sik; Chung, Kee Yang; Choi, Kang-Yell (2015-06-29). "The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing". Journal of Experimental Medicine. 212 (7): 1061–1080. doi:10.1084/jem.20141601. ISSN 1540-9538. PMC 4493411.
  3. ↑ Kim, Hyun‐Yi; Choi, Sehee; Yoon, Ji‐Hye; Lim, Hwan Jung; Lee, Hyuk; Choi, Jiwon; Ro, Eun Ji; Heo, Jung‐Nyoung; Lee, Weontae; No, Kyoung Tai; Choi, Kang‐Yell (April 2016). "Small molecule inhibitors of the Dishevelled‐ CXXC 5 interaction are new drug candidates for bone anabolic osteoporosis therapy". EMBO Molecular Medicine. 8 (4): 375–387. doi:10.15252/emmm.201505714. ISSN 1757-4676. PMC 4818757.
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