Tripeptide-29 (Collagen Peptide)

Fundamentally, tripeptide-29 acts as a building block of larger collagen molecules. In so doing, it can change, by virtue of its amino acid sequence and relative frequency with the collagen superstructure, the tertiary and quaternary properties of a collagen molecule. Collagen is not just a structural protein, but also plays roles in cell adhesion, tissue regulation, and healing. Thus, tripeptide-29 has the potential to impact a multitude of physiologic features.

Tripeptide-29 Research

In vitro research into tripeptide-29 has revealed that the peptide, in its non- polymerized form, is a partial agonists of the collagen receptor GPVI[1]. GPVI is expressed on the surface of platelets, the cell-like structures responsible for the early formation of blood clots. The GPVI receptor plays a crucial role in the collagen-induced activation of platelet aggregation in vascular tissue, a first step to clot formation and tissue repair. Thus, collagen fibers are generally considered thrombogenic.

When dysregulated, collagen thrombogenesis may lead to the development of blood clots. Interestingly, crosslinking of tripeptide-29 appears to boost GPVI activation, suggesting that the peptide could be useful in understanding how to create a “just- right” clotting environment in the setting of various bleeding/clotting disorders.

Tripeptide-29 and Collagen Stability

Benchtop research into the role of short peptides like tripeptide-29 has revealed that they can be used to modulate the stability of collagen. Tripeptide-29, in particular, has helped scientists to understand that the ultimate structure of collagen is influenced most by the last peptide in a tripeptide monomer. In a monomer of A-B-C, it is the peptide in the C position that has most influence on final collagen stability[2]. This finding could help scientists to one day create synthetic implants for cartilage, bone, teeth, and more.

Collagen and Free Radical Damage

Free radical damage is the primary cause of cellular and tissue aging. The body has a number of defenses against free radical damage, but they all become less effective over time.

Research in sea cucumber has revealed that collagen hydrolysates constructed from monomers like tripeptide-29 are effective radical scavengers, and that the structure of the tripeptide monomer can affect scavenger activity. No research has been carried out on Tripeptide 29, yet, but there is interest in determining how such peptides could be used in foods and nutraceutical products[3].

Tripeptide-29 Regulates Tissue Fibrosis

In vitro studies of pig skin, cattle skin, fish scales, and chick feet have revealed that tripeptide-29 is an inhibitor of dipeptidylpeptidase-IV activity[4], [5].

Dipeptidylpeptidase-IV (DPP4) is an enzyme found mostly in cells associated with immune signaling and cell apoptosis. It is an intrinsic part of the cell membrane and indiscriminately destroys growth factors, chemokines, neuropeptides, and vasoactive peptides. It also plays a large role in glucose metabolism by breaking down incretins, hormones that stimulate a decrease in blood glucose levels.

Animal studies have revealed that DPP4 plays a role in the development of fibrosis in organs that include the kidney and liver[5]. Inhibiting the enzyme thus prevents scarring in disease processes that affect these organs. Tripeptide-29 maybe doubly beneficial in this setting, as diabetes is a prime cause of kidney fibrosis. The ability of Tripeptide-29 to stimulate glucose uptake and reduce fibrosis, both by inhibiting DPP4, opens a number of research avenues in the control of not just diabetes, but its pathologic sequelae as well.

Tripeptide-29 and Skin Tone

There is recent interest in the role of tripeptide-29 and other tripeptides in protecting skin against the normal process of aging. Research in animals suggests that topical use of tripeptides can reduce the visible effects of skin aging by improving contour, reducing skin deformation, and boosting hydration. There is also evidence that tripeptides can smooth skin texture and reduce the appearance of brown and red spots. In fact, 90% of subjects in the study showed improved moisturization of the skin in addition to increased flexibility secondary to improve elasticity[6].

When combined with certain hexapeptides, topical tripeptide-29 can boost skin turnover and reduce fine lines, crow’s feet, under eye bags, and eye hollowing. In these animal studies, roughly 50% of subjects showed improved skin appearance with twice daily application of the peptide paste[7].

Reference

1.     J. Asselin, C. G. Knight, R. W. Farndale, M. J. Barnes, and S. P. Watson, “Monomeric (glycine- proline-hydroxyproline)10 repeat sequence is a partial agonist of the platelet collagen receptor glycoprotein VI,” Biochem. J., vol. 339 (Pt 2), pp. 413–418, Apr. 1999.

2.     K. Mizuno, D. H. Peyton, T. Hayashi, J. Engel, and H. P. Bächinger, “Effect of the -Gly- 3(S)-hydroxyprolyl-4(R)- hydroxyprolyl- tripeptide unit on the stability of collagen model peptides,” FEBS J., vol. 275, no. 23, pp. 5830–5840, Dec. 2008.

3.     M. Z. Abedin et al., “Biochemical and radical-scavenging properties of sea cucumber (Stichopus vastus) collagen hydrolysates,” Nat. Prod. Res., vol. 28, no. 16, pp. 1302–1305, 2014.

4.     T. Hatanaka, K. Kawakami, and M. Uraji, “Inhibitory effect of collagen-derived tripeptides on dipeptidylpeptidase-IV activity,” J. Enzyme Inhib. Med. Chem., vol. 29, no. 6, pp. 823–828, Dec. 2014.

5.     H. S. Min et al., “Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction,” Lab. Investig. J. Tech. Methods Pathol., vol. 94, no. 6, pp. 598–607, Jun. 2014.

6.     A. Garre, G. Martinez-Masana, J. Piquero-Casals, and C. Granger, “Redefining face contour with a novel anti-aging cosmetic product: an open-label, prospective clinical study,” Clin. Cosmet. Investig. Dermatol., vol. 10, pp. 473–482, 2017.

7.     Reivitis, K. Karimi, C. Griffiths, and A. Banayan, “A single-center, pilot study evaluating a novel TriHex peptide- and botanical- containing eye treatment compared to baseline,” J. Cosmet. Dermatol., vol. 17, no. 3, pp. 467–470, Jun. 2018.