Ayatollah Ali Khamenei also warned the United States that any "mistake" in its dealings with oil-rich Iran would lead to consequences for global energy supplies.
"We have achieved a lot of scientific goals," Ayatollah Khamenei said in a speech marking the 17th anniversary of the death of Iran's Islamic revolutionary leader, Ayatollah Ruhollah Khomeini..
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"This is an historic investment. It represents our political independence and national self confidence. We should not sell out this precious resource because of the enemies' threats and we should not be fooled by enemy bribes," he said.
The five permanent members of the UN Security Council plus Germany are poised to present Iran with an offer of incentives and the prospect of fresh multilateral talks - involving the United States - on the condition that Iran first suspends uranium enrichment.
That activity is at the centre of fears the country could make nuclear weapons. Iran insists it only wants to make reactor fuel, and not bombs and that enrichment is a right enshrined by the Non-Proliferation Treaty.
Oil supply warning
EU foreign policy chief Javier Solana is expected in Tehran in the coming days to present the proposals. Iran has been given just weeks to make up its mind or else face robust Security Council action including possible sanctions.
However, Ayatollah Khamenei indicated that the offer could end up being dead on arrival by shrugging off any fear of the consequences.
"You threaten Iran. You say you want to direct energy in the region. If you make a single mistake about Iran, the supply of energy will definitely be put in serious risk," Ayatollah Khamenei said of the United States.
Rice responds
US Secretary of State Condoleezza Rice swiftly brushed off the warning. "I think we shouldn't place too much emphasis on a threat of this kind," she told Fox News.
"I think something like 80 per cent of Iran's budget comes from oil revenue, and so obviously it would be a very serious problem for Iran if oil were disrupted on the market."
Diplomats in Vienna revealed that the new package of incentives to be presented to Iran in the next few days included a US offer to lift some of its unilateral sanctions.
But Ms Rice said the deal struck with other major powers also included a promise of tough action if Tehran rejected the package.
Speaking at Khomeini's mausoleum on the southern outskirts of Tehran, Ayatollah Khamenei insisted that "Iran is no threat to anyone".
"They accuse us of developing nuclear bombs. This is an absurd lie. We do not need nuclear weapons and bombs. We don't have any target to use them on. Using nuclear weapons is against Islamic rules," he said.
He also asserted that the United States had been weakened - and his speech was frequently interrupted by chants of "Death to America", "Death to Israel" and "We are ready!" from the thousands of faithful packed into Khomeini's huge mausoleum.
"We do not want war... but you should know that whoever threatens our interests, they will see the sharpness of our wrath."
On the weekend, hardline president Mahmoud Ahmadinejad revealed that in a telephone conversation earlier in the day with UN Secretary
General Kofi Annan, he had been asked "to examine the proposals and not act hastily".
"I said that we will not act hastily and that we will examine the proposals," Mr Ahmadinejad said.