ChemInfo - Chemistry Blog

New chemistry database – organoboron compounds

admin — Thu, 18 Apr 2013 08:39:36 +0000

Organoboron Compounds – chem. database
From website: “Boronic acids and their esters are highly popular synthetic intermediates in organic synthesis for their ease and efficiency of conversion to other functional groups, in metal-catalyzed cross-coupling reactions and for their unique biochemical activity.The palladium-catalyzed cross-coupling reaction of organoboron compounds with organic halides or pseudo-halides – the Suzuki-Miyaura reaction – is a remarkably useful tool in organic synthesis.”
Synthesis references and physical data (melting/boiling point, refractive index, density) for more than 2,000 boronic acids, boronic acid esters and trifluoroborates. You can search for substance by chemical name and CAS number.

New drug candidates for cystic fibrosis

admin — Sun, 06 Nov 2011 22:12:14 +0000

Cystic Fibrosis (CF) affects about 30,000 people in the United States and approximately 70,000 people worldwide. Since the identification of the Cystic Fibrosis gene in 1989, researchers have known that CF results from mutations in the gene for the protein cystic fibrosis trans-membrane conductance regulator (CFTR). Without functioning CFTR, which is an epithelial ion channel, patients have flawed regulation of salt and water absorption and secretion in the lung, liver, pancreas, intestine and reproductive tract. The majority of people with CF in the United States have a specific CFTR mutation, but there are over 1,500 mutations that can cause this multi-system disease, by affecting either the quantity or the quality of CFTR. Approximately 3-5% of patients with Cystic Fibrosis have a missense mutation, G551D, which causes the CFTR protein at the cell surface not to open and close properly.

The question, then: is it possible to change the function of this protein channel itself? In a new report appearing in the FASEB Journal, the researchers describe how they used HT screening to identify small-molecule drug candidates which are able to correct the defects in cystic fibrosis cells, making the cystic fibrosis cell look more like the normal cell.

Cas Registry Number

admin — Sun, 18 Sep 2011 21:20:01 +0000

CAS Registry Numbers are an important tool for substance searching. These are unique identifiers assigned by the Chemical Abstracts Service (CAS) to specific substances identified by them in the chemical literature.

CAS Numbers are not related to chemistry, are unrelated to any previous systems, and do not readily form phonetic analogs or synonyms. The numbers are simple and regular, convenient for database searches.

The format of CAS number is three blocks of numbers divided by hyphens ie. XXX-XX-X. It should will always be read from right to left:

The first block can be between 2 and 6 digits. The second block has only 2 digits and the last block is always a single digit. Any preceding zeros in the first block need to be discarded. For example, the CAS number for formaldehyde is 50-00-0.

Cas numbers save you from having to think of all the different trivial or semisystematic names, synonyms, brand names, or possible systematic names when you are doing a compound search by linking them all into a single search term.

For example, there are over ten synonyms for methanol, e.g., carbinol, methyl hydroxide, methyl alcohol, wood alcohol. The CAS Registry Number for it, 67-56-1, is specific to all those names for the same substance.

Where to find CAS numbers on the Internet? The following free websites can be used:
1) Chemical Synthesis Database
2) Common Chemistry
3) R&D Chemicals
4) Pubchem
5) ChemIDplus

What is a Peptide Library?

admin — Wed, 17 Aug 2011 20:09:25 +0000

The combinatorial peptide library is a powerful method in which a vast number of various peptides are synthesized.

The first use of synthetic peptide libraries was reported by Geysen et al. in 1984, using the pin method, and since then many papers describing different methods of synthesizing and screening peptide libraries have been published.

The combinatorial peptide library approach is mainly based on three methods. In one, peptide libraries are synthesized and cleaved from a solid support to be screened as free compounds. In a second, synthetic combinatorial libraries of peptides are assayed on their solid support. The third method is based on phage-display, which enables selection of clones of interest rather than screening, because large phage libraries can be panned against a target molecule by standard protocols, allowing enrichment of only a few hundred specific phages that can easily be screened for positive ligands in a single test. Specific phages are then treated for DNA sequencing and peptide genes are revealed for subsequent chemical synthesis.

The above three technologies for selection of peptide ligands fall into two groups: libraries that allow the selection of ligands in their final unlabeled and soluble form and those by which peptides are selected while still linked to their support, either synthetic or biological, or to a labeling molecule.

Synthetic combinatorial libraries, especially synthetic peptide libraries, are generally prepared by two different methods, the “divide, couple, recombine” (DCR) method, also referred to as “pool/split, portion/mix, split-and-mix”, and the “amino acid mixture” method. The DCR method involves dividing resin into pools, coupling amino acids to individual aliquots of resin, mixing them and dividing them for next amino acid coupling. This process generates “one-bead one-compound (OBOC)” libraries containing millions of random peptides, each bead expressing only one peptide and each peptide having equal distribution in the library.

The advantage of the OBOC technique – a large number (10⁶−10⁸) of peptides can be synthesized and screened rapidly. One major disadvantage of the OBOC technique – each library compound is tethered to the solid support via a linker such as polyethylene glycol and may result in steric hindrance between the cellular receptor and the library substance.

Chemis3D – Molecular Viewer Applet

admin — Tue, 25 Jan 2011 14:45:53 +0000

Chemis3D is a free Java Applet for the online 3D Visualization of Molecular Models. Small molecules as well as macromolecular structures could be manipulated and rendered in a variety of styles and colors. In addition some useful tools permit the user to label atoms or groups and to measure inter-atomic distances. Chemis3D is a small applet, which is quickly loaded and uses most common chemical file formats (*.xyz, *.mol, *.pdb). Its integration in a Web page is very easy and supports many options.

The Nobel Prize in Chemistry 2010

admin — Thu, 07 Oct 2010 06:15:23 +0000

This year’s Nobel Prize in chemistry was awarded jointly to Richard F. Heck, Ei-ichi Negishi and Akira Suzuki for the development of palladium-catalyzed cross coupling.

Left to Right: Richard F. Heck, Ei-ichi Negishi and Akira Suzuki

General scheme of palladium-catalyzed cross coupling reactions

This chemical tool has vastly improved the possibilities for chemists to create sophisticated chemicals, for example carbon-based molecules as complex as those created by nature itself.

Palladium-catalyzed cross coupling is used in research worldwide, as well as in the commercial production of for example pharmaceuticals and molecules used in the electronics industry.

Browsing the web with chemistry – chemicalize.org

alexa1138 — Thu, 16 Sep 2010 15:17:16 +0000

I write to introduce new functionality on chemicalize.org

chemicalize.org is a public website for adding chemical resolution to web browsing, chemical names and chemical structure files. The service allows you to browse the web and see structures for chemical names (text) identified in the web page. For each chemical structure image generated, you can link through to predicted data from the structure. The service is free and will be useful to anyone wishing to add chemical structures and data to their web browsing experience.

To try the service: Mouse over the dotted underline text on this chemicalized wikipedia page (tho any URL will work), then click on any structure image popup to see predicted data for the structure. See the video on the chemicalize.org landing page

Looking forward to your feedback and I hope you enjoy it.
Alex

Histone deacetylase inhibitors

admin — Sat, 14 Aug 2010 11:49:19 +0000

Histone deacetylases (HDACs) are enzymes that catalyze the deacetylation of lysine residues located in the NH2 terminal tails of core histones, which is associated with transcriptional silencing. There are 18 known human histone deacetylases, grouped into four classes based on the structure of their accessory domains. Class I (HDACs 1-3 and 8), II (HDACs 4-7, 9, and 10), and IV (HDAC 11) enzymes are Zn2+-dependent enzymes and are called HDACs, while class III enzymes (also known as sirtuins) are defined by their dependency on NAD+.

Histone deacetylase inhibitors (HDACis) are emerging as a new class of anticancer drugs and have been shown to alter gene transcription and exert antitumor effects such as growth arrest, differentiation, apoptosis, and inhibition of tumor angiogenesis.

The interest in HDAC inhibitors began almost 30 years ago during some studies designed to understand why DMSO caused terminal differentiation of murine erythroleukemia cells. This early observation paved the way for the development of novel pharmacological agents in the field of chromatin remodeling. In October 2006 the FDA approved the first HDAC inhibitor – Suberoylanilide Hydroxamic Acid (SAHA, Zolinza, Vorinostat) to treat the rare cancer cutaneous T-cell lymphoma (CTCL).

One of the most well-known HDAC inhibitors is a drug called suberoylanilide hydroxamic acid (SAHA)

Based on their chemical structure, histone deacetylase inhibitors inhibitors can be subdivided into four different classes, including hydroxamates, cyclic peptides, aliphatic acids and benzamides. TSA, a compound of hydroxamates, is the first nature product that has been discovered to possess the HDAC inhibitor activity in 1990. Other compounds, for example, CBHA and Panobinostat, have been used in pre- and clinical trials in this group. Another class of HDAC inhibitors is aliphatic acid, including Valproic acid (VPA), phenylbutyrate. The third group is benzamide consisted of Entinostat and MGCD0103. The last group is cyclic peptide including FK-228.

The following HDAC Inhibitors are currently undergoing clinical trials:
Tacedinaline (CI-994, PD-123654, GOE-5549, Acetyldinaline); Entinostat (SNDX-275, MS-27-275, MS-275); BML-210; M344; Dacinostat (LAQ824,NVP-LAQ824); Panobinostat (LBN-589, LBH589, Panobinostat, LBH-589, NVP-LBH589); Mocetinostat (MGCD-0103); Belinostat (PX105684, PXD101); CBHA; PCI-24781 (CRA-024781); ITF2357; Trichostatin A; Apicidin; CUDC-101; Droxinostat; JNJ-26481585; MC1568; SB939; Tubastatin A.

HDAC inhibitors are promising new targeted anti-cancer agents. These substances cause cancer cell growth arrest, differentiation, apoptosis and cell death of a broad spectrum of malignant cells, both solid tumors and hematologic malignancies. Normal cells are much less sensitive to HDAC inhibitors than transformed cells.

References:
1) Jiahuai Tan, et al. Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents. Journal of Hematology & Oncology 2010, 3:5
2) Philip Jones, et al. A Novel Series of Potent and Selective Ketone Histone Deacetylase Inhibitors with Antitumor Activity in Vivo. Journal of Medicinal Chemistry, 2008, 51, 2350–2353.
3) Nancy Zhou, et al. Discovery of N-(2-Aminophenyl)-4-[(4-pyridin-3-ylpyrimidin 2-ylamino)methyl]benzamide (MGCD0103), an Orally Active Histone Deacetylase Inhibitor. Journal of Medicinal Chemistry, 2008, 51, 4072–4075
4) Marielle Paris, et al. Histone Deacetylase Inhibitors: From Bench to Clinic. Journal of Medicinal Chemistry, 2008, 51(6), 1505-29.

What is a Compound Library?

admin — Wed, 14 Jul 2010 18:02:17 +0000

A compound library is a collection of real stored chemicals and/or virtual chemical compounds. The compound library or chemical library can contain stored chemicals each of them has associated data with information such as the chemical structure, purity, quantity, and physiochemical characteristics of the compound. The virtual compound libraries consist of 2D or 3D representations of chemical compounds that are used for diverse purposes using computational methods.
The logical designs of both library types are often similar to one another, and the two methods — experimental (for real compound libraries) and computational (for virtual compound libraries) are often complement one another in drug discovery development process.
What is a purpose of a compound library?
Compound libraries usually used for drug discovery high-throughput screening, a process consisting of testing a large number of chemicals against some assays and/or targets.
Both real and virtual compound libraries are commonly run in parallel in drug discovery campaigns with the results of one compared to the other. The main purpose is to design libraries for promising new drug leads. 20 years ago, the first libraries typically included huge amounts of small-molecule structures; today compound libraries design is more sophisticated than in the past and centers around the methods used for choosing compound membership. The choice of compounds is often based on two widely used design strategies: diversity oriented design and target oriented design. The goal of diversity oriented design strategy is to generate libraries with a highly diverse set of chemical compounds based for example on skeletal diversity, a strategy where the scaffold elements of chemical compounds are chosen to maximize their variation in 3D structure, electrostatics, or molecular properties. A molecular property diversity method include hydrogen bond donors/acceptors, polarizable groups, charge distributions, hydrophobic and lipophobic fragments, and numerous other properties. The diversity of the libraries resulting from these methods is often measured using statistical techniques, such as cluster and principal components analysis. In contrast to diversity, target oriented design seeks to create libraries that are focused around specific chemotypes, molecular species, or classes of compounds. Compound libraries with target oriented design results in focused libraries with a limited number of well-defined structures. To generate focused libraries 3D shape, 3D electrostatics, pharmacophore models, molecular descriptors, and target active sites are used.
Regardless of diversity or target oriented design chemical compounds need to satisfy a variety of constraints before they become marketable drugs, for instance, Lipinski’s rules place limits on molecular weight, the number of hydrogen bond donors and acceptors, the number of rotatable bonds, and solubility. Applying Lipinski’s rules in library design acts as a molecular property filter, you can effectively restrict the set of compounds to those with drug-like characteristics.

Why do we need amino acids?

admin — Thu, 01 Jul 2010 21:47:06 +0000

Although more than 250 amino acids have been found in nature but only twenty of these are required for human growth.
These twenty amino acids are classified into two groups: nonessential and essential.
Essential amino acids must be obtained from the diet. These include threonine, leucine, lysine, methionine, valine, isoleucine, tryptophan, and phenylalanine.
One of the amino acids – histidine is called semi-essential because it is necessary for proper growth in children.
Nonessential amino acids are those that the body can manufacture from the essential amino acids or normal breakdown of proteins. The non-essential amino acids are alanine, arginine, serine, aspartic acid, cysteine, glutamine, asparagine, glycine, glutamic acid, proline and tyrosine.
Amino acids, as the building blocks of the most diverse biological compounds, have a characteristic structure. All twenty amino acids have an amino group and a carboxyl group with a functional group covalently bound to the alpha carbon. In the essential amino acids, the functional groups are used to classify the amino acids into polar, non-polar, or basic side chains.
Here is a closer look at the eight essential amino acids and the important roles they play.

Threonine T (Thr)

Threonine supports the immune system by aiding in the production of antibodies, and since it is found largely in the central nervous system, may be helpful in treating some types of depression. Threonine is an important part of numerous proteins in the body and is required in forming tooth enamel, collagen and elastin, which are responsible for healthy skin and wound healing.

Leucine L (Leu)

Leucine is a very important amino acid and nutritional component because it controls your body’s ability to process protein, vitamins and minerals. If you do not have enough this amino acid in your system, your body will not be able to properly absorb the protein and vitamins that you consume.

Lysine K (Lys)

Lysine helps make carnitine, which converts fatty acids to energy, and it helps form collagen needed for connective tissue and bones.

Methionine M (Met)

Methionine is an intermediate in the biosynthesis of cysteine, carnitine, phosphatidylcholine and other phospholipids. Improper conversion of methionine can lead to atherosclerosis.

Valine V (Val)

Valine is involved in glucose metabolism and also regulates the immune system. Athletes sometimes use L-valine for muscle metabolism and to help speed up recovery time after seriously rigorous exercise.

Isoleucine I (Ile)

This amino acid is needed for the formation of hemoglobin, which carries iron in the blood, and for the regulation of blood sugar, which is burned for energy in the muscles during exercise.

Tryptophan W (Trp)

L-Tryptophan is an essential precursor to a number of neurotransmitters in the brain. This amino acid plays a role in balancing mood and sleep patterns, helps support relaxation and feeling better.

Phenylalanine F (Phe)

Phenylalanine plays a key role in the biosynthesis of other amino acids and is important in the structure and function of many proteins and enzymes. This amino acid is converted to tyrosine, used in the biosynthesis of dopamine and norepinephrine neurotransmitters.
The eight essential amino acids are responsible for a vast array of metabolic, physiologic, and therapeutic effects throughout the body. In addition to their roles in peptide and protein structure, these free amino acids have significant functions as specialized nitrogen containing products, neurotransmitters, and as alternate energy sources.
The amino acids play an important and unique role in the body and therefore they must be obtained from the diet.

The information was taken from the www.aminoacidsguide.com website.

Tags – aminos, amino acids, aminoacid, amino asit