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 (T2D), 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 ...
.
* 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
In chemistry, an amphiphile (), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'', nonpolar) properties. Such a compound is called amphiphilic or amphipathic. Amphiphilic c ...
α-helix
An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix).
The alpha helix is the most common structural arrangement in the Protein secondary structure, secondary structure of proteins. It is al ...
.
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
Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
.
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. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...
'', ''
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
Lysis ( ; from Greek 'loosening') is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ' ...
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
Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-Car ...
residues with
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...
residues and
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...
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 p ...
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
Exenatide, sold under the brand name Byetta among others, is a medication used to treat type 2 diabetes. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after metformin and sulf ...
References
Peptides
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