Glycomimetic is a term used to refer to

molecules A molecule is a group of two or more atoms that are held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemistry ...

that have structures similar to

carbohydrates A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ma ...

, but with some variation. This will normally result in modified biological properties.

Introduction

Often, modification of the structure will take place around the

glycosidic linkage A glycosidic bond or glycosidic linkage is a type of ether bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate. A glycosidic bond is formed between the hemiacetal or hemiketal group o ...

. Replacement of one or other of the glycosidic oxygen atoms by carbon, sulfur, nitrogen etc. will alter the properties of the glycosidic bond. The molecules produced in this way would be called carbasugars or C-glycosides, thiosugars or thioglycosides, or

iminosugars An iminosugar, also known as an iminosaccharide, is any analog of a sugar where a nitrogen atom has replaced the oxygen atom in the ring of the structure. Iminosugars are common components of plants and may be responsible for some of their medici ...

or glycosylamines. When nitrogen is introduced, the glycomimetic may become positively charged at physiological pH, meaning that it may act as an

enzyme inhibitor An enzyme inhibitor is a molecule that binds to an enzyme and blocks its Enzyme activity, activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which Substrate (biochemistry), substrate molecules are converted ...

, either by

Coulombic Coulomb's inverse-square law, or simply Coulomb's law, is an experimental law of physics that calculates the amount of force between two electrically charged particles at rest. This electric force is conventionally called the ''electrostatic f ...

interaction with

carboxylate In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an anion, an ion with negative charge. Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,... ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

side-chains in the enzyme

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate, the ''binding s ...

, or by mimicking positive-charge build-up at the

transition state In chemistry, the transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. It is often marked w ...

of the reaction, or both. Iminosugars (sometimes referred to erroneously as azasugars) are classic examples of molecules with this behaviour. Glycosylamines typically have a lower stability, being easily hydrolysed, which means that to exploit an exocyclic nitrogen substituent at C-1, further modification is necessary. An example of this would be the additional substitution of the ring-oxygen for carbon as is seen in

valienamine Valienamine is a C-7 aminocyclitol found as a substructure of pseudooligosaccharides such as the antidiabetic drug acarbose and the antibiotic validamycin. It can be found in ''Actinoplanes ''Actinoplanes'' is a genus in the family Micromono ...

. Altering the structure of a carbohydrate will normally result in several changes to the properties of the molecule. As well as changing the stability of the glycosidic bond, the ring-conformation may be affected. Also the conformation of the glycosidic bond may be affected. As well as obvious changes in the immediate vicinity of the substitution, e.g. that replacement of an acetal oxygen by methylene (CH2) would result in loss of a

hydrogen-bond In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, covalently bonded to a mo ...

participatory atom, such a substitution is expected to have more subtle effects resulting from a change in the

dipole In physics, a dipole () is an electromagnetic phenomenon which occurs in two ways: * An electric dipole moment, electric dipole deals with the separation of the positive and negative electric charges found in any electromagnetic system. A simple ...

of the molecule, such as slight changes in hydrogen bonding or

pKa In chemistry, an acid dissociation constant (also known as acidity constant, or acid-ionization constant; denoted ) is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction :H ...

values of the unchanged hydroxyl groups. Substitution by CF2 rather than methylene has been explored in efforts to address this and come up with better mimetics while still retaining the hydrolytic stability gained by the modification.

Examples of commercially relevant glycomimetic molecules

Tamiflu

Tamiflu Oseltamivir, sold under the brand name Tamiflu among others, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complicati ...

is a carbocyclic mimic of the cell-surface carbohydrate

sialic acid Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone. The term "sialic acid" () was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this group is ''N''-acetylneuraminic acid ...

. Tamiflu is an enzyme inhibitor that blocks the action of

influenza Influenza, commonly known as the flu, is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These sympto ...

virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...

neuraminidases Exo-α-sialidase (, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids: : Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glycosidic linkag ...

(sialidases).

Acarbose

Acarbose Acarbose ( INN) is an anti-diabetic drug used to treat diabetes mellitus type 2 and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay ( Bayer AG), in North America as Precose ( Bayer Pharmaceuticals), and in ...

is a pseudotetrasaccharide mimicking

maltotetraose Maltodextrin is a name shared by two different families of chemicals. Both families are glucose polymers (also called ''dextrose polymers'' or '' dextrins''), but have little chemical or nutritional similarity. The digestible maltodextrins (or ...

(a substructure of

starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diet ...

). One of the

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

units has been replaced by

- a carbasugar, linked to the next carbohydrate by an amine bridge. Another of the glucose units appears as a 6-deoxy variant. Acarbose is an enzyme inhibitor that is used as a drug against

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 ...

Miglustat

Miglustat Miglustat, sold under the brand name Zavesca among others, is a medication used to treat type I Gaucher disease and Pompe disease. It was approved for medical use in the European Union in November 2002, and for medical use in the United Stat ...

is an

iminosugar An iminosugar, also known as an iminosaccharide, is any analog of a sugar where a nitrogen atom has replaced the oxygen atom in the ring of the structure. Iminosugars are common components of plants and may be responsible for some of their medic ...

in which the ring oxygen is replaced by nitrogen. Miglustat a drug used to treat some rare

lysosomal storage disorder Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other ...

diseases.

References

{{Reflist Molecular biology