A new way to make powerful antibiotics

first_imgAntibiotics have been taking it on the chin lately. Not only has resistance to the medications been growing, but drug companies have been dropping antibiotic research programs because the drugs are difficult and expensive to make. Now, help is on the way. Researchers report today that they’ve found a way to churn out new members of one of the most widely used classes of antibiotics, called macrolides. The work could lead to new weapons against antibiotic-resistant infections, and possibly save millions of lives.Macrolides, drugs that include erythromycin and azithromycin, were first developed in the 1950s. Since then they’ve become a bulwark against bacterial and fungal infections. Chemically, macrolides are giant rings containing 14 to 16 carbon atoms, with one or more sugar appendages dangling off the side. Bacteria synthesize them to fight off their neighbors. Yet bacteria didn’t evolve to make macrolides good drugs in people. So medicinal chemists—the group of researchers who actually build new drugs—start with the natural versions and tweak their bonds one at a time in an effort to make them safer and more effective. But in most cases it’s impossible to confine the changes to just one bond on a large molecule. When multiple bonds react, the result is an unwanted broad mixture of end products, none of which contain just the one specific change desired for making a better drug.  To solve that problem, Harvard University chemist Andrew Myers and colleagues adapted a divide-and-conquer strategy that they had applied to tetracycline antibiotics back in 2005. They started with three basic macrolide ring structures and broke each one down into eight molecular “modules.” They then carefully mapped out reactions needed to put the pieces back together. For two such linkers they even invented new chemical reactions to forge the bonds just so. This allowed them to tinker with the modules individually, and then reassemble them. By repeating the strategy over and over, they forged more than 300 entirely new macrolides. Sign up for our daily newsletter Get more great content like this delivered right to you! Country Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Emailcenter_img Click to view the privacy policy. Required fields are indicated by an asterisk (*) When given to a panel of bacterial lab cultures, several of these compounds showed potent antibiotic activity against antibiotic-resistant microbes, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, the team reports online today in Nature. Perhaps equally important, Myers says, is that all the reactions used for the assembly produce high yields of the final products. That’s essential, he notes, because bacteria don’t produce the starting material for the new compounds. So if any of them proves a valuable medicine, chemists will be able to synthesize large quantities of it cheaply from scratch.“This is a great example of beautiful chemistry that will have a tangible societal benefit,” says Phil Baran, a synthetic organic chemist at the Scripps Research Institute in San Diego, California. Myers has set up a company, Macrolide Pharmaceuticals, to commercialize the work.last_img

Leave a Reply

Your email address will not be published. Required fields are marked *