Both trace to alpha melanocyte stimulating hormone, a thirteen residue peptide derived from proopiomelanocortin that binds the melanocortin receptor family. Melanotan 1, CAS 75921-69-6, is catalogued as afamelanotide and as [Nle4, D-Phe7]-alpha-MSH, meaning the natural sequence with the methionine at position four replaced by norleucine and the phenylalanine at position seven inverted to the D configuration. Melanotan 2, CAS 121062-08-6, is a shortened cyclic analog in which a lactam bridge links side chains within the core message sequence.
The recorded formulas show how much was removed. Melanotan 1 is C78H111N21O19 with an average mass of 1646.85, consistent with a full length linear analog. Melanotan 2 is C50H69N15O9 with an average mass of 1024.18, roughly six hundred daltons lighter, because the analog retains the core melanocortin message motif, discards the flanking residues and closes the remainder into a ring. Neither residue sequence is recorded in our molecular dataset, so both are described here by catalogued analog identity rather than position by position.
Receptor behaviour follows from that structural choice. The melanocortin receptor family has five subtypes, and the melanocortin 1 receptor on pigment cells is the one most studied for the linear analog. Melanotan 1 is described in binding studies as retaining high affinity at that subtype while behaving as a broad agonist across the family. The cyclic analog is described in the literature as potent but notably non selective, engaging melanocortin 1, 3, 4 and 5 receptors, and much of the interest in it as a research tool comes from the melanocortin 4 receptor arm rather than the pigment cell arm. Comparing the two in a cell model therefore requires stating which receptor subtype the cells express.
Stability is where cyclisation earns its keep. A linear peptide presents an open backbone to endopeptidases and two accessible termini to exopeptidases. The D configured phenylalanine in melanotan 1 blocks one common cleavage point, but the chain remains extended and conformationally flexible. The lactam bridge in melanotan 2 constrains the backbone into a fixed ring, which both removes the preferred conformations for protease attack and locks the message residues into the geometry the receptor recognises. In practice the cyclic analog is the more robust of the two in solution, and the linear analog is handled with more care against degradation.
Handling is otherwise similar. Both are lyophilized powders held at minus 20 degrees Celsius protected from light and moisture, reconstituted with gentle swirling, refrigerated at 2 to 8 degrees Celsius once in solution, and aliquoted so that freeze thaw is not repeated. Both are pigment active in cell models, so preparations are protected from light as a matter of routine. Identity for each lot is confirmed by mass spectrometry against the theoretical mass, which is the practical way to tell a 1646.85 species apart from a 1024.18 species.
Selection depends on the receptor subtype in question and on whether backbone flexibility matters to the assay. What remains unsettled is the comparative subtype selectivity picture itself, since reported affinity ratios vary with the receptor construct and species used, and cross study comparison between the linear and cyclic analogs is unreliable for that reason.