Pseudin is a peptide derived from ''
Pseudis paradoxa
''Pseudis paradoxa'', known as the paradoxical frog or shrinking frog, is a species of hylid frog from South America. Its name refers to the very large—up to long—tadpole (the world's longest), which in turn "shrinks" during metamorphosi ...
''.
Pseudins have some antimicrobial function.
There are several different forms:
* pseudin-1
* pseudin-2 -- has been proposed as a treatment for
type 2 diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
.
* pseudin-4
Pseudin-2
Pseudin-2 is the most abundant version of the pseudins found on the skin of the paradoxical frog.
The primary sequence reads as GLNALKKVFQGIHEAIKLINNHVQ. Its secondary/tertiary structure consists of one cationic
amphipathic α-helix
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...
.
Antibacterial activity
Pseudin-2 was shown to have potent antibacterial activity, but a lower cytotoxicity.
The cytotoxicity of a peptide can be measured by its effect on human
erythrocytes.
It takes a lower concentration of Pseudin-2 to kill bacteria or fungi such as ''
E. coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'', ''
S. aureus'', and ''
C. albicans'' than to kill human erythrocytes.
It is hypothesized that Pseudin-2 binding to the cell membrane of the bacteria results in a conformational change in which the peptide forms an α-helical shape, which allows it to perform
cell lysis by inserting itself in the hydrophobic portion of the membrane.
This mechanism is applicable to similar amphipathic α-helical peptides created by many frog species, although most of these peptides aren't very potent against bacteria.
By increasing the cationicity and amphipathic nature of the molecule, it is possible to create analogues of Pseudin-2 that are even more selective towards bacteria. This is done by substituting
leucine residues with
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
residues and
glycine residues with
proline
Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...
residues, which results in two shorter α-helices (linked by the substituted proline) that are more attuned to penetrating bacterial cell membranes.
See also
*
Exenatide
References
Peptides
{{biochem-stub