# Tripeptide-29

> Tripeptide-29 is a collagen-derived tripeptide, glycyl-L-prolyl-(4R)-4-hydroxy-L-proline (Gly-Pro-Hyp), with the formula C12H19N3O5 and a molecular weight of 285.30 g/mol. It is the most characteristic repeating triplet of the collagen triple helix and a major peptide in collagen hydrolysates. Research covers its absorption, metabolism and delivery to skin. It is not an FDA-approved drug.

Canonical: https://peptideproperties.com/compounds/tripeptide-29/

## Identity

- **Class:** Copper & Cosmetic Peptides
- **Molecular formula:** C12H19N3O5
- **Molecular weight:** 285.30 g/mol
- **Monoisotopic mass:** 285.1325 Da
- **CAS number:** 2239-67-0
- **PubChem CID:** 11778669
- **InChIKey:** SZEOBSAZWJLOGY-VGMNWLOBSA-N
- **Sequence notes:** Gly-Pro-Hyp; the third residue is (4R)-4-hydroxy-L-proline (Hyp), a post-translationally modified, non-standard amino acid. Free N-terminal amine and free C-terminal carboxylic acid.

## Key facts

- Class: collagen-derived tripeptide; cosmetic ingredient name tripeptide-29
- Sequence: Gly-Pro-Hyp, with hydroxyproline as the C-terminal residue
- Formula C12H19N3O5; molecular weight 285.30 g/mol (PubChem CID 11778669)
- CAS 2239-67-0; also called collagen tripeptide or glycyl-prolyl-hydroxyproline
- Origin: repeating triplet of the collagen triple helix, released from collagen by enzymatic digestion
- Evidence base: intestinal-transport models, rat and mouse pharmacokinetics, and human plasma studies
- Regulatory status: not approved by the FDA as a drug

## What Is Tripeptide-29?

Tripeptide-29 is the cosmetic ingredient name for Gly-Pro-Hyp, a three-residue peptide of glycine, proline and hydroxyproline that repeats throughout the collagen molecule. It is often called collagen tripeptide, and it is one of the main bioactive candidates studied in collagen hydrolysates.Collagen-derived small peptides such as Gly-Pro-Hyp and its breakdown product Pro-Hyp have been linked to various physiological functions. Because collagen is not readily cleaved into these peptides during digestion, researchers have prepared tripeptide-rich collagen products by targeted enzymatic digestion to study whether the intact tripeptide is absorbed.[1]Most published work on Gly-Pro-Hyp falls into three areas: its role as a structural unit of the collagen triple helix, its stability and transport across the intestinal lining, and its appearance in blood and skin after ingestion of collagen hydrolysates. The sections below summarize each, separating in-vitro, animal and human evidence.

## Chemical Structure and Molecular Identity

Tripeptide-29 is glycyl-L-prolyl-(4R)-4-hydroxy-L-proline, a linear tripeptide with a free N-terminal amine and a free C-terminal carboxylic acid. PubChem (CID 11778669) lists the molecular formula C12H19N3O5 and a molecular weight of 285.30 g/mol. The CAS number is 2239-67-0.Two of the three residues are cyclic imino acids. Proline and hydroxyproline each contain a pyrrolidine ring, which restricts backbone rotation, and hydroxyproline adds a hydroxyl group at the ring's 4-position in the R configuration. Because hydroxyproline is a non-standard amino acid formed by post-translational modification of proline, Gly-Pro-Hyp cannot be written with standard one-letter codes. The molecule is very polar, with a computed XLogP of -4.3.In collagen, the backbone consists of a repeating (Gly-X-Y)n sequence, and Gly-Pro-Hyp is one of the triplets that occur in large numbers. Researchers use repeating Gly-Pro-Hyp units as the host framework in synthetic host-guest peptides that form stable triple helices.[2] Solid-state NMR and molecular modeling studies indicate that abundant Gly-Pro-Hyp triplets confer well-defined flexibility on the collagen triple helix.[3]
### Names and synonyms

- Cosmetic ingredient name: tripeptide-29
- Chemical names: glycyl-prolyl-hydroxyproline, H-Gly-Pro-Hyp-OH
- Common names: collagen tripeptide, GPH, Gly-Pro-Hyp

## Research History and Development

Gly-Pro-Hyp was first studied as a building block of collagen structure and later as a food-derived bioactive peptide. Structural biologists recognized that only a limited set of the more than 400 possible Gly-X-Y triplets occur in significant numbers in collagens, and used Gly-Pro-Hyp repeats as a stable host to measure how other triplets affect triple-helix stability.[2]Interest in the free tripeptide grew from nutrition research. A 2007 study using porcine intestinal brush-border membrane vesicles described Gly-Pro-Hyp as a frequently occurring collagen sequence postulated to have bioactivity, and examined how it is handled at the intestinal surface.[4] In 2016, researchers prepared a collagen tripeptide product from fish scales using collagenase from a nonpathogenic Bacillus species to increase the yield of Gly-Pro-Hyp and Pro-Hyp, and compared its absorption with a high-molecular-weight collagen peptide in rats.[1]Later work traced the tripeptide into blood and skin after ingestion of tripeptide-rich collagen hydrolysate[5] and, in 2024, reported the first individual pharmacokinetic profile of pure Gly-Pro-Hyp in rats.[6]

## Mechanisms Studied in Research

Mechanistic research on tripeptide-29 centers on how it is digested, transported and converted to the dipeptide Pro-Hyp, rather than on a specific receptor. Several studies show that Gly-Pro-Hyp and Pro-Hyp are closely linked metabolically.
### Intestinal hydrolysis and transport
In porcine brush-border membrane vesicles, Gly-Pro-Hyp was degraded over time into free glycine and Pro-Hyp, consistent with removal of the N-terminal glycine by membrane-bound aminopeptidase N. The resulting Pro-Hyp entered the vesicles in a pH-dependent manner that was inhibited by the competing substrate Gly-Pro, indicating uptake by the H+-coupled peptide transporter PEPT1. In this model, Gly-Pro-Hyp did not cross the apical membrane intact, and Pro-Hyp was highly resistant to further hydrolysis.[4]A different picture emerged in a cell-monolayer model: Gly-Pro-Hyp and Pro-Hyp were stable in gastrointestinal fluid and rat plasma for two hours, and Gly-Pro-Hyp was transported across an intestinal cell monolayer.[1] The two findings come from different experimental systems and suggest that both intact transport and hydrolysis may contribute.
### Conversion to Pro-Hyp
In rats, Pro-Hyp formed from Gly-Pro-Hyp behaved similarly to Pro-Hyp given alone, and the authors observed flip-flop kinetics, which they attributed to slow, probably transporter-mediated absorption.[6] In mice, administration of pure Gly-Pro-Hyp led to Pro-Hyp enrichment in the skin, indicating that skin Pro-Hyp can be derived from hydrolysis of the tripeptide.[5]

## Key Findings From Published Studies

Published studies show that Gly-Pro-Hyp from collagen hydrolysates reaches the bloodstream in humans and animals, has low but measurable oral bioavailability in rats, and is converted to Pro-Hyp in tissues including skin. Findings by model are summarized below.
### In vitro and ex vivo

- In porcine brush-border membrane vesicles, Gly-Pro-Hyp was partially hydrolyzed to Pro-Hyp, which was then taken up via PEPT1.[4]
- Gly-Pro-Hyp remained stable in gastrointestinal fluid and rat plasma for two hours and crossed an intestinal cell monolayer.[1]
### Animal studies

- In rats, Gly-Pro-Hyp and Pro-Hyp were better absorbed and reached higher plasma levels after oral administration of a collagen tripeptide preparation than after a high-molecular-weight collagen peptide.[1]
- In a rat pharmacokinetic study using intravenous and intragastric administration, the absolute oral bioavailability of Gly-Pro-Hyp was 4.4%, compared with 19.3% for Pro-Hyp; Gly-Pro-Hyp showed higher first-pass metabolism, a double-peak plasma profile after oral administration, and 5.9% urinary recovery after intravenous administration.[6]
- In mice, ingested Gly-Pro-Hyp appeared in plasma and skin, with Pro-Hyp more enriched in skin.[5]
### Human studies
After ingestion of a collagen hydrolysate high in tripeptides, researchers identified 17 types of collagen-derived peptides transiently in human plasma, with particular enrichment of Gly-Pro-Hyp.[5] In a 12-week randomized, double-blind, placebo-controlled trial in 64 adults, a low-molecular-weight collagen peptide containing more than 15% Gly-X-Y tripeptides, including 3% Gly-Pro-Hyp, was associated with significantly higher skin hydration, improved wrinkle parameters and improvement in two of three elasticity measures versus placebo, with no test-material-related adverse symptoms reported.[7] That trial tested a peptide mixture, so its results cannot be attributed to Gly-Pro-Hyp alone.Because Gly-Pro-Hyp is readily cleaved to Pro-Hyp, researchers typically verify tripeptide identity and purity with HPLC and mass spectrometry certificates of analysis.Because Gly-Pro-Hyp is readily cleaved to Pro-Hyp, researchers typically verify tripeptide identity and purity with HPLC and mass spectrometry certificates of analysis.

## Regulatory and Research Status

Tripeptide-29 is not approved by the US Food and Drug Administration as a drug for any indication. It appears as a component of collagen hydrolysates and as a cosmetic ingredient, and it has an FDA Unique Ingredient Identifier (UNII X6346H6PUM), which is a registration code rather than an approval.As a research compound, pure Gly-Pro-Hyp is used to study collagen-derived peptide absorption, metabolism and tissue distribution, and repeating Gly-Pro-Hyp units remain a standard tool in collagen structural biology.[2][6]Open questions include how much intact Gly-Pro-Hyp, as opposed to Pro-Hyp, reaches target tissues in humans, how intestinal hydrolysis and intact transport compare in vivo, and whether effects reported for tripeptide-containing collagen mixtures can be reproduced with the isolated tripeptide.

## FAQ

**Is tripeptide-29 the same as collagen tripeptide?**
Tripeptide-29 is the cosmetic ingredient name for Gly-Pro-Hyp (glycyl-prolyl-hydroxyproline), which is often called collagen tripeptide. Note that commercial collagen tripeptide products are usually collagen hydrolysates enriched in Gly-X-Y tripeptides rather than pure Gly-Pro-Hyp. One trial, for example, used a collagen peptide with more than 15% tripeptide content, of which 3% was Gly-Pro-Hyp.

**What is the molecular weight of tripeptide-29?**
PubChem lists tripeptide-29 (CID 11778669) with a molecular weight of 285.30 g/mol and the molecular formula C12H19N3O5. Its CAS number is 2239-67-0 and its InChIKey is SZEOBSAZWJLOGY-VGMNWLOBSA-N. The IUPAC name describes a glycyl-prolyl unit linked to (2S,4R)-4-hydroxyproline. Commercial material may be supplied as a salt or with residual solvent, which changes the weight of the bulk solid relative to the free peptide.

**Is Gly-Pro-Hyp absorbed intact?**
Partly. In rats, the absolute oral bioavailability of pure Gly-Pro-Hyp was 4.4%, lower than that of Pro-Hyp, and it showed higher first-pass metabolism. Porcine brush-border membrane studies found it was hydrolyzed to Pro-Hyp before uptake, while a cell-monolayer study found intact transport. In humans, Gly-Pro-Hyp has been detected in plasma after ingestion of tripeptide-rich collagen hydrolysate.

**How is tripeptide-29 different from Pro-Hyp?**
Tripeptide-29 (Gly-Pro-Hyp) is a tripeptide, while Pro-Hyp is the dipeptide left when the N-terminal glycine is removed. Studies show Gly-Pro-Hyp is converted to Pro-Hyp at the intestinal brush border and in tissues. In mice, pure Gly-Pro-Hyp led to Pro-Hyp enrichment in skin, and in rats Pro-Hyp had higher oral bioavailability than the tripeptide.

**Is tripeptide-29 FDA approved?**
No. Tripeptide-29 is not approved by the FDA as a drug for any condition. It is found in collagen hydrolysates and used as a cosmetic ingredient, and pure Gly-Pro-Hyp is supplied as a research compound for laboratory studies of collagen peptide absorption and metabolism. Its FDA UNII code, X6346H6PUM, is an identifier, not an approval.

**What does the research on tripeptide-29 show?**
Research shows that Gly-Pro-Hyp from collagen hydrolysates appears in human plasma, reaches plasma and skin in mice, and is partly converted to Pro-Hyp. In rats its oral bioavailability was 4.4%. A 12-week human trial of a collagen peptide mixture containing Gly-Pro-Hyp reported improved skin hydration and wrinkle measures, but did not test the tripeptide alone.

## References

1. Sontakke SB, Jung JH, Piao Z, et al. Orally Available Collagen Tripeptide: Enzymatic Stability, Intestinal Permeability, and Absorption of Gly-Pro-Hyp and Pro-Hyp. Journal of agricultural and food chemistry 2016. PMID: 27573716
2. Ramshaw JA, Shah NK, Brodsky B. Gly-X-Y tripeptide frequencies in collagen: a context for host-guest triple-helical peptides. Journal of structural biology 1998. PMID: 9724608
3. Goldberga I, Li R, Duer MJ. Collagen Structure-Function Relationships from Solid-State NMR Spectroscopy. Accounts of chemical research 2018. PMID: 29931970
4. Aito-Inoue M, Lackeyram D, Fan MZ, et al. Transport of a tripeptide, Gly-Pro-Hyp, across the porcine intestinal brush-border membrane. Journal of peptide science : an official publication of the European Peptide Society 2007. PMID: 17554807
5. Yazaki M, Ito Y, Yamada M, et al. Oral Ingestion of Collagen Hydrolysate Leads to the Transportation of Highly Concentrated Gly-Pro-Hyp and Its Hydrolyzed Form of Pro-Hyp into the Bloodstream and Skin. Journal of agricultural and food chemistry 2017. PMID: 28244315
6. Won J, Kang J, Noh K, et al. Pharmacokinetics of collagen dipeptides (Gly-Pro and Pro-Hyp) and tripeptides (Gly-Pro-Hyp) in rats. Journal of food science 2024. PMID: 38051020
7. Kim DU, Chung HC, Choi J, et al. Oral Intake of Low-Molecular-Weight Collagen Peptide Improves Hydration, Elasticity, and Wrinkling in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients 2018. PMID: 29949889