This is a working overview of Reversed-phase HPLC, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-03-28. Anything still debated is marked as such rather than presented as settled.
Published studies examine a fairly narrow set of endpoints. Rodent experiments commonly measure maze learning, infarct volume after induced ischemia, and tissue levels of neurotrophic factors. Clinical reports from Russian centres describe attention, memory and recovery scores in patients after stroke or transient ischemic attack. Most of those human studies are small and few have been repeated by independent groups. Outcome measures differ between studies, which limits direct comparison.
Circulation time for the peptide is short because peptidases cleave it readily. The Pro-Gly-Pro tail is thought to slow breakdown compared with the bare ACTH fragment, but the gain appears modest. Absorption after intranasal dosing is limited, and only a fraction of a dose is expected to reach the central nervous system. Laboratory concentrations therefore sit well above levels achieved systemically, a gap that complicates translation from bench findings to clinical claims.
Semax is normally supplied as a lyophilized powder, and that form is the most stable. Suppliers commonly recommend storage at -20 °C in a desiccated container protected from light, with short-term handling at room temperature limited to weighing and transfer. Powder that has absorbed moisture degrades faster, so vials should be warmed to ambient temperature before opening to prevent condensation on the contents. Hygroscopic behavior is typical of short hydrophilic peptides, and humidity control matters more than temperature alone for long-term retention.
Once dissolved, the peptide is considerably less stable than the solid. Aqueous solutions are usually prepared at neutral to slightly acidic pH, filtered, and divided into single-use aliquots before freezing. Repeated freeze-thaw cycles are a common cause of avoidable loss and are best prevented by never refreezing a thawed aliquot. Adsorption to plastic and glass surfaces can lower the measured concentration of dilute solutions, particularly below roughly 0.1 mg/mL. Buffer choice, salt content, and container material all influence how much peptide remains detectable after storage.
Identity and purity are established with standard peptide methods. Reversed-phase HPLC with ultraviolet detection near 214 nm resolves the parent peak from deletion and truncation byproducts, and reports typically quote a main-peak percentage. Mass spectrometry by electrospray or MALDI-TOF confirms the expected molecular mass, while amino acid analysis or peptide mapping can verify composition when the sequence itself is in question. A certificate of analysis that pairs a chromatogram with a mass spectrum is more informative than a purity figure alone. Counter-ion content and residual solvents are separate specifications and are frequently omitted.
| Property | Value | Notes |
|---|---|---|
| Appearance | White to off-white powder | Lyophilized solid from research suppliers |
| Solubility | Freely soluble in water | Also dissolves in aqueous buffers; solutions are used fresh |
| Typical storage temperature | -20 °C for lyophilized powder | Short-term transport at 2-8 °C is common |
| Common analytical method | Reverse-phase HPLC | Paired with mass spectrometry for identity confirmation |
| Common synonyms | ACTH(4-10) analogue; MEHFPGP | N-terminal methionine retained in the chain |
Stability depends heavily on physical state. Lyophilized powder held dry, cold and dark retains its content over long periods, whereas dissolved peptide begins to change within days at room temperature. The most cited degradation route is oxidation of the methionine residue, which converts the peptide to a sulfoxide form that elutes differently on chromatography. Hydrolysis of amide bonds and adsorption onto container walls contribute smaller losses. Buffers that exclude oxygen from the headspace slow the oxidation pathway, but no single condition prevents all change indefinitely.
Practical handling follows from those properties. Bulk material is best divided into single-use portions soon after receipt, because each thaw exposes the whole container to moisture and temperature cycling. Vials should be allowed to reach room temperature before opening to prevent condensation on the powder. Low-binding plasticware reduces loss of dilute solutions, and sterile filtration is used when a preparation must remain free of microbial growth. Records of batch number, reconstitution date and storage history are what allow a later analytical result to be interpreted meaningfully.
Identity and purity of Semax are established mainly by reversed-phase high-performance liquid chromatography coupled with mass spectrometry. The chromatographic trace gives a purity estimate as a percentage of total peak area, while electrospray or matrix-assisted laser desorption ionization confirms the molecular mass against the calculated value. Amino acid analysis and sequence-specific fragmentation provide further confirmation when a supplier's chain of custody is unclear. Vendors frequently quote a purity figure without stating the detection wavelength or the integration method, which limits how far one number can be compared with another.
Identity and purity of semax are established with reversed-phase high-performance liquid chromatography coupled to ultraviolet detection, usually at 214 nanometres. Mass spectrometry, most often electrospray ionisation in positive mode, confirms the molecular mass and reveals truncated sequences. Amino acid analysis and peptide mapping after enzymatic digestion provide additional structural confirmation. Laboratories typically report purity as the percentage area of the main peak, a figure that does not capture isomeric or oxidised variants unless the method resolves them.
The peptide is prone to several degradation pathways. Oxidation of the methionine residue produces a sulfoxide that elutes close to the parent peak in many chromatographic systems. Hydrolysis of peptide bonds and deamidation of susceptible residues in related sequences also reduce purity over time. Lyophilised material kept dry at minus twenty degrees Celsius and shielded from light is the most stable form commonly described in laboratory practice.
Material sold for laboratory use varies widely in stated purity and documentation. A certificate of analysis should list the analytical method, the column and detector used, and the observed purity value. Independent verification by an outside laboratory is the practical way to confirm identity when documentation is absent or internally inconsistent. Regulatory status differs by country, and a product legal in one jurisdiction may be unapproved or controlled in another.
Bruce Glick grew up in Pittsburgh, Pennsylvania and was interested in birds as a child. His father, Peter Glick, was the Secretary of Labor for Pennsylvania. Glick served in World War II. He went to Rutgers University and studied birds majoring in poultry science, graduating in 1951. In 1950 he married Kay McCall. He received an M.S. degree from the University of Massachusetts in genetics in 1952 and attended Ohio State University as a Ph.D. student, graduating with a PhD in physiology in 1955. While there, he worked on determining the purpose of the Bursa of Fabricius, a gland that he was able to remove from a goose without any apparent effect. A fellow graduate student, Timothy Chang, worked with Glick's geese in a different study, and noticed that the birds without the Bursa of Fabricius did not produce expected antibodies. Glick and Chang wrote up the results of this study and were unable to get it published in Science, so it was published in Poultry Science in 1956. Their publication, considered a landmark paper, is one of the most cited works from Poultry Science.
Depending on the surroundings the optimal pH varies from 8 in the cytoplasm to 8.3 in the nucleus. The GLD-2 protein together with 136 proteins more, is involved in the molecular process of hematopoietic progenitor cell differentiation, in the human proteome. This is the process in which precursor cell type acquires the specialized features of a hematopoietic progenitor cell, a kind of cell types including myeloid progenitor cells and lymphoid progenitor cells.
=== Unstable isotopes === The suitable half-life and decay mode made lutetium-176 used as a pure beta emitter, using lutetium which has been exposed to neutron activation, and in lutetium–hafnium dating to date meteorites. The isotope 177Lu emits low-energy beta particles and gamma rays and has a half-life around 7 days, positive characteristics for commercial applications, especially in therapeutic nuclear medicine. The synthetic isotope lutetium-177 bound to octreotate (a somatostatin analogue), is used experimentally in targeted radionuclide therapy for neuroendocrine tumors. Lutetium-177 is used as a radionuclide in neuroendocrine tumor therapy and bone pain palliation. Lutetium (177Lu) vipivotide tetraxetan is a therapy for prostate cancer, FDA approved in 2022.
Sources: en.wikipedia.org
=== Metalloprotein–ligand interactions === The primary sequences of thousands of olfactory receptors are known from the genomes of more than a dozen organisms: they are seven-helix transmembrane proteins, but there are very few solved structures. Their sequences exhibit typical class A GPCR motifs, useful for building their structures with molecular modeling. Golebiowski, Ma and Matsunami showed that the mechanism of ligand recognition, although similar to other non-olfactory class A GPCRs, involves residues specific to olfactory receptors, notably in the sixth helix. There is a highly conserved sequence in roughly three quarters of all ORs that is a tripodal metal ion binding site, and Suslick has proposed that the ORs are in fact metalloproteins (mostly likely with zinc, copper and possibly manganese ions) that serve as a Lewis acid site for binding of many odorant molecules. Crabtree, in 1978, had previously suggested that Cu(I) is "the most likely candidate for a metallo-receptor site in olfaction" for strong-smelling volatiles which are also good metal-coordinating ligands, such as thiols. Zhuang, Matsunami and Block, in 2012, confirmed the Crabtree/Suslick proposal for the specific case of a mouse OR, MOR244-3, showing that copper is essential for detection of certain thiols and other sulfur-containing compounds. Thus, by using a chemical that binds to copper in the mouse nose, so that copper was not available to the receptors, the authors showed that the mice could not detect the thiols.
== Awards == Vincent du Vigneaud Award for Excellence in Peptide Science (2000) American Chemical Society's Ralph F. Hirschmann Award in Peptide Chemistry (2004) Bruce Merrifield Award (2005) Fellow of the American Association of Pharmaceutical Scientists (2006) Dan K. Richardson Entrepreneurship Program's 2011 Entrepreneur of the Year
Early in his second tenure, Mahathir visited Japan and Indonesia to reaffirm good relations, and reignited a water dispute with Singapore. By the end of 2018, several disputes over maritime and airspace borders with Singapore had continued. Mahathir met twice with president Rodrigo Duterte in his first year in office to strengthen cooperation with the Philippines on a broad range of security, economic and political issues. Mahathir again prioritised relations with Japan and strengthened economic and defence ties with Russia. He visited Vladivostok for a meeting of the Eastern Economic Forum in late 2019, where he cast doubt on the Joint Investigation Team's findings related to the downing of Malaysia Airlines Flight 17. Mahathir called the murder charges brought to four Russians related to the flight "ridiculous", calling it "a political issue on how to accuse Russia of wrongdoing". Malaysia launched a foreign policy framework in late 2019. In response to European Union regulations phasing out palm-oil based biofuels, Mahathir discussed bringing a formal complaint to the World Trade Organization or a case to the European Court of Justice with Indonesian president Joko Widodo. Mahathir condemned the killing of Saudi journalist Jamal Khashoggi in October 2018 and the assassination of Iranian General Qasem Soleimani by the United States in 2020. Mahathir was supportive of the 2018–19 Korean peace process. He also indicated that Malaysia would re-open its embassy in North Korea, which had remained closed since the 2017 assassination of Kim Jong-nam.
== Nucleotide excision repair == As illustrated above, (+)-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) forms bulky covalent DNA adducts with guanines. Most of these adducts can be efficiently eliminated from DNA by the process of nucleotide excision repair. Those adducts that are not removed can cause errors during DNA replication leading to carcinogenic mutations.
Sources: en.wikipedia.org
It consists mainly of animal experiments and small clinical reports, with much of the clinical material published in Russian-language journals. Large independent trials are scarce. Separating reliable effects from chance findings is consequently difficult.
A fraction of an intranasal dose is thought to reach the central nervous system, and this route is favoured partly for that reason. The proportion is not well characterized. Direct measurement in humans remains difficult with current methods.
Raised BDNF and NGF expression has been reported across several animal studies, which makes the signal fairly consistent. Whether the same change occurs in humans at usable doses is not established. It is best treated as a working hypothesis rather than a confirmed clinical mechanism.
Each freeze-thaw cycle can degrade a fraction of the peptide and promote aggregation. Dividing a stock solution into single-use volumes removes repeated cycling as a variable. It also limits the time a thawed solution spends at room temperature.