Chemical Platform for the Preparation of Synthetic Orally Active Peptidomimetics with Hemoregulating Activity.
Deigin. Vladislav V; Ksenofontova. Olga O; Khrushchev. Alexey A; Yatskin. Oleg O; Goryacheva. Alexandra A; Ivanov. Vadim V
Key Findings
- A branched piperazine‑2,5‑dione (diketopiperazine) scaffold can carry peptide fragments and make them orally bioavailable.
- Three out of five thymogen‑based analogues showed strong hemostimulatory (blood‑forming) effects in live mice and in irradiated bone‑marrow cell assays.
- The platform could be used to develop other peptide‑based drugs for oral use.
Practical Outcomes
- For now, there’s no ready‑to‑use oral thymogen supplement for humans. The study suggests that with further development, oral versions of thymogen or similar peptides might become feasible, potentially offering a convenient way to support blood and immune health. Biohackers should watch for follow‑up studies before trying any self‑experimentation.
Summary
Researchers created a new chemical method to turn short peptide drugs like thymogen (Glu‑Trp) into pills that can be taken by mouth. They made five versions of the drug, and three of them boosted blood‑forming activity in mice and in bone‑marrow cells taken from irradiated mice. This shows the concept works, but it’s still early‑stage animal work.
Abstract
A novel chemical platform based on branched piperazine-2,5-dione derivatives (2,5-diketopiperazines) for creating orally available biologically active peptidomimetics has been developed. The platform includes a diketopiperazine scaffold with "built-in" functionally active peptide fragments covalently attached via linkers. The concept was applied to two hemostimulatory drugs, the dipeptide thymogen (GluTrp) and the tripeptide stemokin (IleGluTrp). Preparation of a series of respective derivatives is described. Of the five synthesized analogues, three demonstrated high hemostimulatory activity in vivo on intact mice and on ex vivo irradiated bone marrow cells. Prospects of further development of the concept are discussed.
Study Information
pubmed
2016
2016-07-26T00:00:00.000Z
10.1002/cmdc.201600157
14
13