The sanctions, announced a week after the UN Security Council imposed fresh penalties on Tehran, target insurance companies, oil firms and shipping lines linked to Iran's atomic or missile programs.
And they also take broader aim at Iran's Islamic Revolutionary Guards Corps (IRGC), which US Secretary of State Hillary Clinton has accused of supplanting the government of Iran and turning it into a military dictatorship.
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Among the individuals sanctioned are Iran's defense minister Ahmad Vahidi.
"Our actions today are designed to deter other governments and foreign financial institutions from dealing with these entities and thereby supporting Iran's illicit activities," Treasury Secretary Timothy Geithner said.
Geithner told reporters that Iran's Post Bank -- the 16th Iranian-owned bank added to the blacklist -- was designated for its alleged support of proliferation activities.
The measures also target the IRGC Air Force and IRGC Missile Command, which are suspected of having ties to Iran's ballistic missile program, according to the Treasury Department.
Also targeted:
-- Rah Sahel and Sepanir Oil and Gas Engineering Co. "for their ties to previously designated Khatam al-Anbiya Construction Headquarters.
-- Two individuals for their roles in the IRGC.
-- Two individuals and two entities for their ties to Iran's WMD programs, including Javedan Mehr Toos, a procurement broker for Kalaye Electric Company.
-- Five Islamic Republic of Iran Shipping Lines (IRISL) front companies.
Among the other individuals sanctioned are Javad Karimi Sabet, who has been linked to the Atomic Energy Organization of Iran, and Mohammad Ali Jafari, the commander in chief of the IRGC since September 2007.
Geithner said the Obama administration has identified a total of 22 petroleum, energy and insurance companies located both inside and outside Iran "that are owned or controlled by the Iranian government."
Under the actions taken, "all transactions involving any of the designees and any US person are prohibited, and any assets the designees may have under US jurisdiction are frozen," the Treasury Department said.
The Obama administration had promised to take further steps of its own and called on other countries to do the same after the UN Security Council last week slapped its four set of sanctions on Tehran in four years.
"We need other countries to move with us," Geithner said.
"So alongside our efforts to build international support for new sanctions, we have been working behind the scenes, building international support among finance ministries, for additional actions to prevent abuse of the global financial system by Iran," he said.
European Union foreign ministers already on Monday proposed new sanctions going further than UN restrictions.
The measures, which also cover the oil and gas industry, with transport and banking or insurance curbs, will now go forward to an EU summit in Brussels on Thursday for final approval.
The foreign ministers who met in Luxembourg said the EU would seek to prohibit new investment as well as the transfers of technologies, equipment and services.
Howard Berman, chairman of the House Foreign Affairs Committee, welcomed the new US sanctions, saying they will "significantly extend the reach of comprehensive Iran sanctions legislation that Congress will soon pass."
Tehran says its nuclear program is purely for civilian purposes, but Israel and Western powers fear it may be trying to develop nuclear weapons that would tip the balance of power in the Middle East.
